Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]3)[CH2:3][CH2:2]1.[CH3:18][O:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][NH2:25])=[CH:22][CH:21]=1>>[CH3:18][O:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][N:25]2[CH2:6][CH2:5][N:4]([C:7]3[CH:8]=[C:9]4[C:14](=[CH:15][CH:16]=3)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]4)[CH2:3][CH2:2]2)=[CH:22][CH:21]=1
Reactant: COc1ccc(CN)cc1
Reactant: O=C1CCc2cc(N3CCOCC3)ccc2N1
Product: COc1ccc(CN2CCN(c3ccc4c(c3)CCC(=O)N4)CC2)cc1
Yield: 10 %

Procedure:
A mixture of 2.32 g of 6-morpholino-3,4-dihydrocarbostyril and 14.7 g of 4-methoxybenzylamine was placed in a sealed tube and heated at 170° to 200° C. for 5 hours. Excessive 4-methoxybenzylamine was distilled off under reduced pressure and the residue was isolated and purified through silica gel column chromatography followed by recrystallization from ethanol to give 0.35 g of 6-[4-(4-methoxybenzyl)-1-piperazinyl]-3,4-dihydrocarbostyril, m.p. 196°-198° C., colorless needles.
Reaction SMILES: [C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:19][O:20][CH2:21][CH2:22][NH:23][C:24]1[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][N:25]=1>>[CH3:19][O:20][CH2:21][CH2:22][NH:23][C:24]1[N:25]=[CH:26][C:27]([NH:30][C:12]([C:10]2[N:11]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:8][C:9]=2[C:15]([F:18])([F:17])[F:16])=[O:14])=[CH:28][CH:29]=1
Reactant: O=C(O)c1nc(-c2ccccc2)oc1C(F)(F)F
Reactant: COCCNc1ccc(N)cn1
Product: COCCNc1ccc(NC(=O)c2nc(-c3ccccc3)oc2C(F)(F)F)cn1

Procedure:
With a procedure similar to example 16 above, 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [6-(2-methoxy-ethylamino)-pyridin-3-yl]-amide was prepared from 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid and N2-(2-methoxy-ethyl)-pyridine-2,5-diamine. LCMS calcd for C19H17F3N4O3 (m/e) 406, obsd 407 (M+H).
Reaction SMILES: C([O:5][C@H:6]([CH3:43])[C@@H:7]([C:16]1[O:20][N:19]=[C:18]([C@@H:21]2[CH2:25][C:24](=[N:26][O:27][CH3:28])[CH2:23][N:22]2[C:29]([C:31]2[CH:36]=[CH:35][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:33][CH:32]=2)=[O:30])[N:17]=1)[NH:8]C(OC(C)(C)C)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>>[CH3:28][O:27][N:26]=[C:24]1[CH2:25][C@@H:21]([C:18]2[N:17]=[C:16]([C@@H:7]([NH2:8])[C@H:6]([OH:5])[CH3:43])[O:20][N:19]=2)[N:22]([C:29]([C:31]2[CH:32]=[CH:33][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:35][CH:36]=2)=[O:30])[CH2:23]1
Reactant: CON=C1C[C@@H](c2noc([C@@H](NC(=O)OC(C)(C)C)[C@@H](C)OC(C)(C)C)n2)N(C(=O)c2ccc(-c3ccccc3)cc2)C1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CON=C1C[C@@H](c2noc([C@@H](N)[C@@H](C)O)n2)N(C(=O)c2ccc(-c3ccccc3)cc2)C1
Yield: 30 %

Procedure:
4-{[(2S,4EZ)-2-(5-{(1S,2R)-2-tert-butoxy-1-[(tert-butoxycarbonyl)amino]propyl}-1,2,4-oxadiazol-3-yl)-4-(methoxyimino)pyrrolidinyl]carbonyl}-1,1′-biphenyl (100 mg, 1.80 mmol) was treated with a 25% TFA/DCM solution at 0° C. for 1 hour. The reaction was then made basic with a sodium carbonate solution (10%) and extracted with DCM. The organic phases were combined and dried over magnesium sulfate and solvent removal afforded a residue, which was purified by flash-chromatography using dichloromethane/methanol as eluent to give the desired product, (3EZ,5S)-5-{5-[(1S,2R)-1-amino-2-hydroxypropyl]-1,2,4-oxadiazol-3-yl}-1-([1,1′-biphenyl]-4-ylcarbonyl)-3-pyrrolidinone O-methyloxime, as a mixture of E-/Z-isomers in 30% yield (90.3% purity by HPLC).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=1)=O.[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][N:17]=1.C(=O)([O-])O.[Na+]>>[Br:22][C:19]1[CH:20]=[CH:21][C:16]2[N:17]([CH:2]=[C:3]([C:5]3[CH:14]=[CH:13][C:12]4[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=4)[CH:6]=3)[N:15]=2)[CH:18]=1
Reactant: Nc1ccc(Br)cn1
Reactant: O=C(CBr)c1ccc2ccccc2c1
Agent: O=C([O-])O
Agent: [Na+]
Product: Brc1ccc2nc(-c3ccc4ccccc4c3)cn2c1
Yield: 127.9 %

Procedure:
By carrying out the process as in Example 1, and starting from 0.5 g of 2-bromo-1-(naphthalen-2-yl)ethanone, 0.72 g of 2-amino-5-bromopyridine and 0.29 g of sodium hydrogen carbonate, 0.83 g of 6-bromo-2-(naphthalen-2-yl)imidazo[1,2-a]pyridine is obtained. Mp=226-228° C.
Reaction SMILES: [NH2:1][CH:2]([C:4]1[N:9]=[N:8][C:7]([NH:10][C:11]2[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=2)=[N:6][CH:5]=1)[CH3:3].C(N(CC)CC)C.[N+:30]([C:33]1[CH:41]=[CH:40][CH:39]=[CH:38][C:34]=1[C:35](Cl)=[O:36])([O-:32])=[O:31]>ClCCl>[N+:30]([C:33]1[CH:41]=[CH:40][CH:39]=[CH:38][C:34]=1[C:35]([NH:1][CH:2]([C:4]1[N:9]=[N:8][C:7]([NH:10][C:11]2[CH:12]=[C:13]([O:21][CH3:22])[C:14]([O:19][CH3:20])=[C:15]([O:17][CH3:18])[CH:16]=2)=[N:6][CH:5]=1)[CH3:3])=[O:36])([O-:32])=[O:31]
Reactant: O=C(Cl)c1ccccc1[N+](=O)[O-]
Reactant: COc1cc(Nc2ncc(C(C)N)nn2)cc(OC)c1OC
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(Nc2ncc(C(C)NC(=O)c3ccccc3[N+](=O)[O-])nn2)cc(OC)c1OC
Temperature: 25 °C
Reaction time: 1 h
Yield: 26.4 %

Procedure:
To a stirred solution of 6-(1-aminoethyl)-N-(3,4,5-trimethoxyphenyl)-1,2,4-triazin-3-amine (Intermediate 9) (0.30 g, 1.0 mmol) in dichloromethane (10 mL) cooled to −78° C. was added triethylamine (0.42 mL, 3.0 mmol) and 2-nitrobenzoyl chloride (0.35 mL, 1.5 mmol). After stirring for one hour, the solution was quenched with water and allowed to warm to room temperature. The solution was diluted with dichloromethane (50 mL) and washed with 0.1N HCl (2×50 mL) and brine (50 mL). The solution was dried with magnesium sulfate and filtered, and silica gel (5 g) was added to the solution, followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to a gradient elution using ethyl acetate:hexane (20:80) to ethyl acetate:hexanes (100:0) using a RediSep silica gel cartridge (12 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give 2-nitro-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (0.12 g) as a white solid. MS m/z455 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](O)=[O:8])=[C:5]([N+:12]([O-])=O)[CH:4]=1.ClC(OCC(C)C)=O>O1CCCC1>[NH2:12][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:11]=[CH:10][C:6]=1[CH2:7][OH:8]
Reactant: COc1ccc(C(=O)O)c([N+](=O)[O-])c1
Agent: CC(C)COC(=O)Cl
Solvent: C1CCOC1
Product: COc1ccc(CO)c(N)c1
Temperature: -15 °C
Reaction time: 0.08 h
Yield: 23.5 %

Procedure:
To a solution of commercially available 4-methoxy-2-nitrobenzoic acid (4.0 g, 20.66 mmol) in tetrahydrofuran (20 mL) at −15° C. under nitrogen was added N-methylmorphorine (2.2 ml, 20 mmol) followed by isobutyl chloroformate (2.6 mL, 20 mmol) in portions. After 5 min, the reaction was filtered and the solid was rinsed with tetrahydrofuran (20 mL). The filtrate was cooled to −15° C. and a solution of sodium borohydride in water (3 M, 10 mL) was added to the filtrate. The reaction was stirred for 5 min. The reaction mixture was partitioned between water and dichloromethane, and extracted aqueous layer with dichloromethane (3×100 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was redissolved in tetrahydrofuran (35 mL) and added palladium (10% on carbon, 400 mg) and stirred under hydrogen gas for 18 hours. The reaction mixture was then filtered through celite and concentrated under reduced pressure. The residue was chromatographed on silica gel with hexanes/ethyl acetate (3:2) gave 744 mg (24% yield) of product as a yellow solid.
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.[C:13]([OH:19])(=[O:18])[CH2:14][CH:15]([CH3:17])[CH3:16].[CH2:20]([O:27][C:28]([N:30]1[C@@H:34]([CH2:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[C@H:33]([CH2:42]I)[O:32][C:31]1([CH3:45])[CH3:44])=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[Cl-].[NH4+]>CCCCCC.C1COCC1.CN(C)P(N(C)C)(N(C)C)=O>[CH2:20]([O:27][C:28]([N:30]1[C@@H:34]([CH2:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[C@H:33]([CH2:42][CH:14]([CH:15]([CH3:17])[CH3:16])[C:13]([OH:19])=[O:18])[O:32][C:31]1([CH3:44])[CH3:45])=[O:29])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CC1(C)O[C@@H](CI)[C@H](CC2CCCCC2)N1C(=O)OCc1ccccc1
Reactant: CC(C)CC(=O)O
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CC(C)C(C[C@@H]1OC(C)(C)N(C(=O)OCc2ccccc2)[C@H]1CC1CCCCC1)C(=O)O
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A 1.6 M solution of butyllithium in hexane (7.8 ml) was added to a stirred solution of diisopropylamine (1.26 g) in dry THF (10 ml) at 0° C. under an atmosphere of argon. The temperature was maintained at 0° C. for 30 minutes, and then a solution of iso-valeric acid (0.63 g) in dry THF (5 ml) was added. The solution was heated at 35° C. for 30 minutes and then cooled to ambient temperature. Hexamethylphosphoramide (HMPA) (1.11 g) was added followed by a solution of (5R,4S)-3-benzyloxycarbonyl-4-cyclohexylmethyl-5-iodomethyl-2,2-dimethyl-1,3-oxazolidine (obtained as described in J.Med.Chem., 1988, 31, 1839) (589 mg) in dry THF (5 ml). The solution was stirred for 2 hours and was then added to saturated ammonium chloride solution (50 ml). The mixture was extracted with ethyl acetate (3×30 ml). The combined extracts were washed with water (30 ml), saturated sodium chloride solution (30 ml) and dried (MgSO4). The solvent was removed by evaporation to give crude (2RS)-2-[(4S,5S)-3-benzyloxycarbonyl-4-cyclohexylmethyl-2,2-dimethyl-1,3-oxazolidin-5-yl]methyl-3-methylbutanoic acid (I), as a clear oil (551 mg), which was used without further purification. For the purposes of characterisation a sample was purified by flash chromatography eluting with ethyl acetate/hexane (1:4 v/v); NMR (CDCl3): 0.8-2.1 (complex m, 28H), 2.3, 2.6 (both m, integration ratio 1:1, total 1H). 3.75 (m, 1H). 3.9 (m, 1H), 5.1 (m, 2H), 7.4 (m, 5H).
Reaction SMILES: Cl[CH2:2]/[CH:3]=[CH:4]/[C:5]([N:7]1[C:12]2=[CH:13][C:14]3[C:15]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([F:30])=[C:26]([Cl:31])[CH:25]=4)=[C:16]([C:21]#[N:22])[CH:17]=[N:18][C:19]=3[CH:20]=[C:11]2[O:10][CH2:9][CH2:8]1)=[O:6].BrC/C=C/[C:36]([N:38]1C2=CC3C(NC4C=CC(F)=C(Cl)C=4)=C(C#N)C=NC=3C=C2OC[CH2:39]1)=O.C(N(CC)C(C)C)(C)C.CNC.C(=O)(O)[O-].[Na+]>CN(C)C=O.O1CCCC1.[Cl-].[Na+].O>[Cl:31][C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][C:27]=1[F:30])[NH:23][C:15]1[C:14]2[CH:13]=[C:12]3[N:7]([C:5](=[O:6])/[CH:4]=[CH:3]/[CH2:2][N:38]([CH3:39])[CH3:36])[CH2:8][CH2:9][O:10][C:11]3=[CH:20][C:19]=2[N:18]=[CH:17][C:16]=1[C:21]#[N:22]
Reactant: N#Cc1cnc2cc3c(cc2c1Nc1ccc(F)c(Cl)c1)N(C(=O)/C=C/CCl)CCO3
Reactant: N#Cc1cnc2cc3c(cc2c1Nc1ccc(F)c(Cl)c1)N(C(=O)/C=C/CBr)CCO3
Agent: CNC
Agent: O=C([O-])O
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)C/C=C/C(=O)N1CCOc2cc3ncc(C#N)c(Nc4ccc(F)c(Cl)c4)c3cc21
Reaction time: 1 h
Yield: 52 %

Procedure:
An amount of the mixture 1-[(2E)-4-chloro-2-butenoyl]-9-(3-chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile and 1-[(2E)-4-bromo-2-butenoyl]-9-(3-chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile (0.708 g, 1.458 mmol), was dissolved in N,N-dimethylformamide (1.89 mL), and to this was added N,N-diisopropylethylamine (0.303 mL, 1.75 mmol), and 0.875 mL (1.75 mmol) of a 2.0 M solution of dimethylamine in tetrahydrofuran The reaction mixture was stirred for one hour, stored for 16 hours in the refrigerator, and then stirred with saturated sodium bicarbonate solution and brine. The solid was filtered off and washed with acetone to give a beige product (372 mg, 52% yield); m.p. 199-200° C.; 1H NMR (DMSO-d6) δ 9.70 (bs, 1H), 8.52 (s, 1H), 8.44 (bs, 1H), 7.47-7.37 (m, 3H), 7.25-7.23 (m, 1H), 6.86-6.79 (m, 1H), 6.62-6.57 (d, 1H), 4.44 (t, 2H), 4.06 (t, 2H), 3.02 (d, 2H), 2.06 (s, 6H); HRMS (Cl) m/z 466.1440 (M+1). Analysis for C24H21ClFN5O2.1.4H2O: Found: C, 60.48; H, 4.85; N, 14.49; F, 4.02; Cl, 7.52. Calcd: C, 60.28; H, 4.73; N, 14.66; F, 3.98; Cl, 7.32.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][NH:8][S:9]([CH3:12])(=[O:11])=[O:10].F[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21]>C(#N)C>[CH3:7][N:8]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21])[S:9]([CH3:12])(=[O:11])=[O:10]
Reactant: CNS(C)(=O)=O
Reactant: O=[N+]([O-])c1ccccc1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: CN(c1ccccc1[N+](=O)[O-])S(C)(=O)=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 55.3 %

Procedure:
To a suspension of cesium carbonate (20.2 g, 0.065 mol) in acetonitrile (500 mL) at room temperature was added N-methylmethanesulfonamide (5.33 g, 0.049 mol) and 1-fluoro-2-nitrobenzene (4.59 g, 0.033 mol) dropwise over 10-15 minutes. The reaction was stirred at room temperature for 12 hours. Upon completion, the mixture was filtered and then concentrated. The residue was purified by silica gel chromatography (dichloromethane) to afford the product N-methyl-N-(2-nitrophenyl)methanesulfonamide (4.2 g, yield 56.1%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.92-7.94 (dd, 1H, J=1.2 Hz, 8.0 Hz), 7.74-7.81 (m, 2H), 7.57-7.62 (m, 1H), 3.27 (s, 3H), 3.03 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.Cl.Cl[CH2:12][C:13]1[CH:14]=[C:15]([CH:28]=[CH:29][CH:30]=1)[O:16][CH2:17][C:18]1[CH:27]=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:12][C:13]2[CH:14]=[C:15]([CH:28]=[CH:29][CH:30]=2)[O:16][CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=2)=[CH:5][CH:4]=1
Reactant: ClCc1cccc(OCc2ccc3ccccc3n2)c1
Reactant: COc1ccc(O)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CC(C)=O
Product: COc1ccc(OCc2cccc(OCc3ccc4ccccc4n3)c2)cc1
Yield: 56.5 %

Procedure:
A mixture of 1.2 g (0.01 mol) 4-methoxyphenol, 3.2 g (0.01 mol) 2-(3-chloromethylphenoxymethyl)quinoline hydrochloride,, 2.8 g (0.02 mol) potassium carbonate and 2.8 g (0.017 mol) potassium iodide in 100 ml acetone was refluxed over a period of 24 hours. Reaction mixture was concentrated to dryness and slurried into water and extracted with ether. The ether extract was washed with water, dried over MgSO4 and concentrated to dryness under reduced pressure to obtain solid. Recrystallization from isopropanol yielded 2.1 g product, m.p. 83°-85° C.
Reaction SMILES: C(Cl)Cl.[Cl:4][C:5]1[N:10]=[C:9]2[S:11][C:12]([SH:14])=[N:13][C:8]2=[CH:7][CH:6]=1.Br[CH:16]([C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)[C:17]([OH:19])=[O:18]>C(N(CC)CC)C>[Cl:4][C:5]1[N:10]=[C:9]2[S:11][C:12]([S:14][CH:16]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[C:17]([OH:19])=[O:18])=[N:13][C:8]2=[CH:7][CH:6]=1
Reactant: O=C(O)C(Br)c1ccc(Cl)cc1
Reactant: Sc1nc2ccc(Cl)nc2s1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(O)C(Sc1nc2ccc(Cl)nc2s1)c1ccc(Cl)cc1
Yield: 68.2 %

Procedure:
A methylene chloride solution of 6.0 g (0.03 m) of 5-chloro-2-mercaptothiazolo[5,4-b]pyridine, 7.5 g (0.03 m) α-bromo-α-(p-chlorophenyl)acetic acid and 6.0 g (0.06 m) triethylamine is heated to gentle reflux overnight. The solution is extracted twice with a dilute hydrochloric acid solution and then once with water. After drying over anhydrous MgSO4, the solvent is removed and the residual solid is recrystallized from acetonitrile. 7.5 g (68% yield) of title compound, melting at 144°-6° C., is obtained.
Reaction SMILES: [C:1]1([CH2:7][C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:10](Cl)[CH3:11].[OH-].[Na+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[C:1]1([CH:7]([CH2:10][CH3:11])[C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: N#CCc1ccccc1
Reactant: CCCl
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Product: CCC(C#N)c1ccccc1
Yield: 90 %

Procedure:
Makosza et al. also studied the alkylation of phenylacetonitrile using quaternary ammonium salts as a catalyst, but satisfactory yields and purity could not be obtained. For example, they reported in Roczniki Chem. Vol. 39, 1223 (1965) and Chemical Abstracts Vol. 64, 12595 (1965) that when phenylacetonitrile is alkylated at room temperature with ethyl chloride in the presence of a 50% aqueous sodium hydroxide solution using benzyltriethyl ammonium chloride as a catalyst, 2-phenylbutyronitrile is obtained at a yield of 90%. The purity of the product was not disclosed, however.
Reaction SMILES: [CH3:1][C:2]([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH:15]([CH3:18])[CH2:16][CH3:17])=[CH:10][CH:9]=1)(C)[C:3]([NH2:5])=O.O.Cl>C1COCC1>[CH3:18][CH:15]([O:14][C:11]1[CH:12]=[CH:13][C:8]([O:7][CH:2]([CH3:1])[CH2:3][NH2:5])=[CH:9][CH:10]=1)[CH2:16][CH3:17]
Reactant: CCC(C)Oc1ccc(OC(C)(C)C(N)=O)cc1
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: CCC(C)Oc1ccc(OC(C)CN)cc1
Reaction time: 48 h

Procedure:
To the above propanamide (1.32 g, 5.6 mmol) in 10 ml of THF at 0° is added dropwise 0.97 M BH3 -THF (35 ml) over 40 min. The solution is heated under reflux overnight and is then allowed to sit at RT for 48 hours, after which 10 ml of water is added dropwise over 30 min., followed by dropwise addition of 20 ml of aqueous 5N HCl. The THF is removed by distillation, and the aqueous phase is saturated with NaOH pellets and extracted with ether (3×). The combined organic layers are washed with water and with brine, dried and solvent removed to give 2-[4-(1-methylpropoxy)phenoxy]propylamine.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[Cl:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[C:10]=1[N:16]=[C:17]=[O:18]>C1(C)C=CC=CC=1>[Cl:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[C:10]=1[NH:16][C:17]([NH:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1)=[O:18]
Reactant: O=C=Nc1c(Cl)cccc1Cl
Reactant: Nc1ccncc1
Solvent: Cc1ccccc1
Product: O=C(Nc1ccncc1)Nc1c(Cl)cccc1Cl
Temperature: 110 °C
Reaction time: 4 h

Procedure:
4-Aminopyridine (100 mg, 1.06 mmol) and 2,6-dichlorophenyl isocyanate (219.7 mg, 1.17 mmol) were dissolved in toluene, and the mixture was then stirred at 110° C. for 4 hr.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.Cl[C:11]1[CH:23]=[C:15]2[N:16]([CH:20]([CH3:22])[CH3:21])[CH2:17][CH2:18][CH2:19][N:14]2[C:13](=[O:24])[N:12]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:11]2[CH:23]=[C:15]3[N:16]([CH:20]([CH3:21])[CH3:22])[CH2:17][CH2:18][CH2:19][N:14]3[C:13](=[O:24])[N:12]=2)=[CH:4][CH:3]=1
Reactant: OCc1ccc(Cl)cc1
Reactant: CC(C)N1CCCn2c1cc(Cl)nc2=O
Product: CC(C)N1CCCn2c1cc(OCc1ccc(Cl)cc1)nc2=O

Procedure:
The title compound or its salt was prepared by a procedure similar to that described for E2 starting from (4-chlorophenyl)methanol and 8-chloro-1-isopropyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([OH:12])=O)=[O:7])=[CH:4][CH:3]=1.[CH3:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]2([OH:7])[C:8]3[C:9](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:10](=[O:12])[N:26]2[CH2:25][C:24]2[CH:27]=[CH:28][C:21]([O:20][CH3:19])=[CH:22][CH:23]=2)=[CH:17][CH:18]=1
Reactant: O=C(O)c1ccccc1C(=O)c1ccc(Cl)cc1
Reactant: COc1ccc(CN)cc1
Product: COc1ccc(CN2C(=O)c3ccccc3C2(O)c2ccc(Cl)cc2)cc1
Yield: 52.3 %

Procedure:
The named compound was synthesised from 2-(4-chlorobenzoyl)-benzoic acid (2.0 g, 7.6 mmol) and 4-methoxy benzylamine (0.542 mL, 4.18 mmol) using General Procedure B, purified by chromatography (Biotage SP4; 10-80% EtOAc/hexane) and obtained as a white solid (0.830 g, 57%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([O:7][CH2:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3][CH2:2]1.[CH:16]1[CH:21]=[CH:20][C:19]([CH2:22][C@H:23]([NH:27][C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[C:24](O)=[O:25])=[CH:18][CH:17]=1>>[CH2:31]([O:30][C:28]([NH:27][C@H:23]([C:24]([N:1]1[CH2:2][CH2:3][CH:4]([O:7][CH2:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:6]1)=[O:25])[CH2:22][C:19]1[CH:18]=[CH:17][CH:16]=[CH:21][CH:20]=1)=[O:29])[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: O=C(N[C@@H](Cc1ccccc1)C(=O)O)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)COC1CCNCC1
Product: CC(C)(C)OC(=O)COC1CCN(C(=O)[C@H](Cc2ccccc2)NC(=O)OCc2ccccc2)CC1
Yield: 96.8 %

Procedure:
By reacting 2.15 g of t-butyl 4-piperidinyloxyacetate with 3.0 g of Z-L-phenylalanine, as described in Example 2b), there are obtained 4.8 g of t-butyl [[1-(N-benzyloxycarbonyl-3-phenyl-L-alanyl)-4-piperidinyl]oxy]acetate MS (FAB): 497 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:10][O:9]2)=[CH:4][N:3]=1.[NH2:11][CH2:12][CH2:13][OH:14].CCOC(C)=O.C1COCC1>C1COCC1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH:8]([OH:9])[CH2:10][NH:11][CH2:12][CH2:13][OH:14])=[CH:6][CH:7]=1
Reactant: NCCO
Reactant: Clc1ccc(C2CO2)cn1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: OCCNCC(O)c1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of (RS)-2-chloro-5-(oxiran-2-yl)pyridine (4.0 g) in THF (15 ml) was added 2-aminoethanol (15.4 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was then poured into EtOAc/THF (1:1) and the mixture was washed with saturated brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to afford (RS)-1-(6-chloropyridin-3-yl)-2-(2-hydroxyethylamino)ethanol (5.05 g) as a yellow solid which was used in the next step without further purification. MS (ISP): 219.3 ([{37Cl}M+H]+), 217.2 ([{35Cl}M+H]+), 201.3 ([{37Cl}M+H—H2O]+), 199.1 ([{35Cl}M+H—H2O]+).
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][N:20]=3)[CH:17]=[N:16][CH:15]=2)[CH:6]=[C:7]([N+:11]([O-:13])=[O:12])[C:8]=1[O:9]C>Br>[N+:11]([C:7]1[CH:6]=[C:5]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][N:20]=3)[CH:17]=[N:16][CH:15]=2)[CH:4]=[C:3]([OH:2])[C:8]=1[OH:9])([O-:13])=[O:12]
Reactant: COc1cc(-c2cncn2-c2ccc(C(F)(F)F)cn2)cc([N+](=O)[O-])c1OC
Agent: Br
Product: O=[N+]([O-])c1cc(-c2cncn2-c2ccc(C(F)(F)F)cn2)cc(O)c1O
Temperature: 25 °C

Procedure:
2-(5-(3,4-dimethoxy-5-nitrophenyl)-1H-imidazol-1-yl)-5-(trifluoromethyl)pyridine (0.394 g, 1 mmol) was heated at 140° C. in 48% aqueous hydrogen bromide (6 mL) for 2.5 hours. The dark homogeneous solution was cooled to room temperature and volatiles were removed by evaporation to leave a pale brown crystalline solid that was dried over P2O5 under vacuum. Trituration of the resulting solid with diethyl ether gave 3-nitro-5-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-imidazol-5-yl)benzene-1,2-diol as a yellow crystalline solid, 0.263 g (72%).