Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([CH:17]=[CH2:18])[C:10]([F:16])=[C:11]([F:15])[C:12]=3[F:14])[C:7](=[O:19])[C:6]([C:20]([O:22]CC)=[O:21])=[CH:5]2)[CH2:3][CH2:2]1.O.S(=O)(=O)(O)O>C(O)(=O)C>[CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([CH:17]=[CH2:18])[C:10]([F:16])=[C:11]([F:15])[C:12]=3[F:14])[C:7](=[O:19])[C:6]([C:20]([OH:22])=[O:21])=[CH:5]2)[CH2:3][CH2:2]1
Reactant: C=Cc1c(F)c(F)c(F)c2c1c(=O)c(C(=O)OCC)cn2C1CC1
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: O
Product: C=Cc1c(F)c(F)c(F)c2c1c(=O)c(C(=O)O)cn2C1CC1
Temperature: 25 °C
Yield: 75.6 %

Procedure:
3 g of the product of Example A are refluxed for 1.5 hours in a mixture of 40 ml of glacial acetic acid, 2 ml of water and 0.6 ml of concentrated sulphuric acid. The reaction mixture is then treated with 40 ml of water and cooled to room temperature. The product is filtered off with suction, washed with water and dried. 2.08 g of the title compound are obtained (75% of theory).
Reaction SMILES: [CH:1]1([NH2:4])[CH2:3][CH2:2]1.C(O)(=O)C.[C:9]([C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)(=O)[CH2:10][CH3:11].C([BH3-])#N.[Na+]>CO>[CH:1]1([NH:4][CH:9]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[CH2:10][CH3:11])[CH2:3][CH2:2]1
Reactant: CCC(=O)c1ccncc1
Reactant: NC1CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CCC(NC1CC1)c1ccncc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 66.7 %

Procedure:
To a mixture of 8 g of molecular sieves and 8.4 g (148 mmol) of cyclopropylamine in 100 ml of methanol at 0° C., were successively added 11 ml of acetic acid and 10 g (74 mmol) of 4-propionyl-pyridine. The reaction mixture was stirred for 3 hrs at reflux and cooled to room temperature. A solution of 6.9 g (185 mmol) of sodium cyanoborohydride in 20 ml of methanol was added dropwise. The reaction mixture was stirred for 3 hrs at reflux, and cooled to room temperature. The reaction mixture was concentrated in vacuum to half its volume and diluted with 80 ml of dichloromethane. Heptane was added so that a solid precipitated. The solid was filtrated. The filtrate was concentrated in vacuum to give 8.7 g (66%) of N-cyclopropyl-1-pyridin-4-yl-propylamine.
Reaction SMILES: [N+:1]([C:4]1[CH:14]=[CH:13][C:7]([CH2:8][P:9](=[O:12])([OH:11])[OH:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:15][C:16]([CH3:21])([CH2:19]O)[CH2:17]O>>[CH3:15][C:16]1([CH3:21])[CH2:19][O:11][P:9](=[O:10])([CH2:8][C:7]2[CH:13]=[CH:14][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[O:12][CH2:17]1
Reactant: O=[N+]([O-])c1ccc(CP(=O)(O)O)cc1
Reactant: CC(C)(CO)CO
Product: CC1(C)COP(=O)(Cc2ccc([N+](=O)[O-])cc2)OC1

Procedure:
With 4-nitrobenzylphosphonic acid and 2,2-dimethyl-1,3-propanediol, the same procedure as in Reference Example 11 was followed, to yield 5,5-dimethyl-2-(4-nitrobenzyl)-1,3,2-dioxaphosphorinane-2-oxide, which was then recrystallized from ethanol-hexane to yield colorless plates having a melting point of 176° to 177° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][N:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:8]=2[N:9]=[C:10](Br)[CH:11]=1)=[O:5])[CH3:2].[O:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[O:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]([CH3:16])=[N:14][N:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:8]=2[N:9]=[C:10]([C:33]2[CH:34]=[CH:35][C:30]([O:29][CH:24]3[CH2:25][CH2:26][CH2:27][CH2:28][O:23]3)=[CH:31][CH:32]=2)[CH:11]=1)=[O:5])[CH3:2]
Reactant: OB(O)c1ccc(OC2CCCCO2)cc1
Reactant: CCOC(=O)c1cc(Br)nc2c1c(C)nn2C1CCCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: O
Product: CCOC(=O)c1cc(-c2ccc(OC3CCCCO3)cc2)nc2c1c(C)nn2C1CCCCO1
Temperature: 85 °C
Reaction time: 1.5 h
Yield: 92.3 %

Procedure:
To a mixture of 6-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (6.00 g), 4-(tetrahydro-2H-pyran-2-yloxy)-phenylboronic acid (4.34 g) and potassium carbonate (2.93 g) in DME/water (v/v=2/1, 200 mL) was added at r.t. under Ar-atmosphere palladium(0) bis(tri-tert-butylphosphine) (0.42 g) and the mixture was stirred at 85° C. for 90 min. To the mixture water was added and it was extracted with ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate, and concentrated in vacuo. The resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate) to give 3-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (7.00 g, 92%). This material was dissolved in isopropanol (30 mL), and 1N sodium hydroxide solution (15 mL) was added. The solution was stirred overnight, then the mixture was contentrated in vacuo to about a third of its volume. The precipitated solid was isolated by filtration and dried in air giving the sodium salt of 3-methyl-1-(tetrahydro-pyran-2-yl)-6-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (6.2 g, 87%).
Reaction SMILES: C([O:8][C:9]1[C:18]([CH3:19])=[C:17]2[C:12]([C:13]([OH:31])=[C:14]([C:21](=[O:30])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[C:15](=[O:20])[O:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1.Br.O>C(O)(=O)C>[OH:31][C:13]1[C:12]2[C:17](=[C:18]([CH3:19])[C:9]([OH:8])=[CH:10][CH:11]=2)[O:16][C:15](=[O:20])[C:14]=1[C:21](=[O:30])[NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=1
Reactant: Cc1c(OCc2ccccc2)ccc2c(O)c(C(=O)Nc3cccc(F)c3)c(=O)oc12
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: Cc1c(O)ccc2c(O)c(C(=O)Nc3cccc(F)c3)c(=O)oc12
Temperature: 100 °C
Yield: 27.4 %

Procedure:
To a solution of the compound of Step A (471 mg, 1.12 mmol) in acetic acid (10 ml) was added hydrobromic acid (48%, 5 ml). The mixture was refluxed at 100° C. for 18 hours. After cooling to room temperature, the reaction mixture was poured into water and a precipitate formed. After filtration, the solid was washed with water and then crystallized from dioxane-methanol. The title product was obtained as a white crystalline solid, mp 287°-289° C., (94.9 mg, 0.307 mmol, yield 27.4%). Analysis: Calculated for C17H12NO5F: C, 62.01 ; H, 3.65; N, 4.26. Found: C, 6204; H, 3.65; N, 4.34. 1H NMR (DMSO-d6): 7.74 (d, J=8.70 Hz, 1H), 7.65 (d, J=11.3 Hz, 1H), 7.43 (m, 1H), 7.40 (m, 1H), 7.04 (m, 1H), 6.98 (d, J=8.70 Hz, 1H), 2.26 (s, 3H).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]#[N:17].Cl.N1C=CC=CC=1.[C:25]([NH2:34])(=[O:33])[C:26]1[C:27](=[CH:29][CH:30]=[CH:31][CH:32]=1)[NH2:28]>C(OCCO)C>[C:16]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:28][C:27]1[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=1[C:25]([NH2:34])=[O:33])=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH3:15])[CH:7]=2)#[N:17]
Reactant: COc1cc2ncc(C#N)c(Cl)c2cc1OC
Reactant: NC(=O)c1ccccc1N
Agent: Cl
Solvent: CCOCCO
Solvent: c1ccncc1
Product: COc1cc2ncc(C#N)c(Nc3ccccc3C(N)=O)c2cc1OC
Yield: 83.9 %

Procedure:
Using an analogous procedure to that described in Example 286, 248.7 mg (1 mmol) of 4-chloro-6,7-dimethoxy-3-quinolinecarbonitrile in 12 mL of 2-ethoxyethanol and in the presence of 115.6 mg (1 mmol) of pyridine hydrochloride was reacted with 177.0 mg (1.3 mmol) of anthranilamide to give 292.4 mg (84.0%) of the product as a deep yellow solid, m.p. 238-240.5° C., mass (electrospray, m/e): M+H 348.9.
Reaction SMILES: Cl.[NH:2]([C:6]1[CH:15]=[C:14]2[C:9]([C:10]([CH2:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)=[N:11][N:12]=[C:13]2O)=[CH:8][CH:7]=1)[C:3]([CH3:5])=[O:4].O=P(Cl)(Cl)[Cl:26].C([O-])(O)=O.[Na+]>C(#N)C.O>[NH:2]([C:6]1[CH:15]=[C:14]2[C:9]([C:10]([CH2:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)=[N:11][N:12]=[C:13]2[Cl:26])=[CH:8][CH:7]=1)[C:3]([CH3:5])=[O:4]
Reactant: O=P(Cl)(Cl)Cl
Reactant: CC(=O)Nc1ccc2c(Cc3ccncc3)nnc(O)c2c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: CC(=O)Nc1ccc2c(Cc3ccncc3)nnc(Cl)c2c1
Temperature: 10 °C
Reaction time: 0.25 h

Procedure:
Under a nitrogen atmosphere, a suspension of 2.24 g (7.6 mmol) 7-acetamino-1-hydroxy-4-(4-pyridylmethyl)phthalazine hydrochloride (ml -oxo-4-[pyridyl-(4′)-methyl]-7-acetamino-1,2-dihydrophthalazine hydrochloride: for preparation see German Auslegeschrift no. 1 061 788 [published 23.07.1959]) in 22 ml acetonitrile is spiked with 1.74 ml (19 mmol) phosphoroxychloride and heated for 4 h to 95° C. The mixture is cooled to 10° C., and 7.5 g NaHCO3 in 30 ml water is added. The deep-red suspension is stirred for 15 min, filtered, and washed out with water. Drying under HV yields the title compound: HPLC: tRet(Grads-40)=10.2; FAB MS (M+H)+=313.
Reaction SMILES: [O:1]=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][NH:5][C:4]2[CH:13]=[CH:14][C:15]([CH2:17][C:18]([OH:20])=[O:19])=[CH:16][C:3]1=2.[CH2:21](O)[CH3:22].S(=O)(=O)(O)O>>[O:1]=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][NH:5][C:4]2[CH:13]=[CH:14][C:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][C:3]1=2
Reactant: O=C(O)Cc1ccc2c(c1)C(=O)c1ccccc1CN2
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)Cc1ccc2c(c1)C(=O)c1ccccc1CN2

Procedure:
5,6-Dihydro-11-oxodibenz[b,e]azepine-2-acetic acid was esterified with ethanol-sulfuric acid in a customary manner to obtain ethyl 5,6-dihydro-11-oxodibenz[b,e]azepine-2-acetate.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([I:10](=[O:12])=[O:11])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[F:13][C:14]([F:19])([F:18])[C:15]([O-])=[O:16].F[P-](F)(F)(F)(F)F.[K+]>O>[F:13][C:14]([F:19])([F:18])[C:15]([O:11][I:10]([C:7]1[CH:8]=[CH:9][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=1)([C:7]1[CH:8]=[CH:9][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=1)=[O:12])=[O:16]
Reactant: O=C([O-])C(F)(F)F
Reactant: CC(C)c1ccc(I(=O)=O)cc1
Agent: F[P-](F)(F)(F)(F)F
Agent: [K+]
Solvent: O
Product: CC(C)c1ccc(I(=O)(OC(=O)C(F)(F)F)c2ccc(C(C)C)cc2)cc1

Procedure:
Bis(4-isopropylphenyl)iodosyl trifluoroacetate is prepared by a similar method to that described by F. M. Beringer and P. Boedlander, loc. cit.) using 4-isopropyliodoxybenzene (8.3 g) as starting material. The trifluoroacetate is dissolved in boiling water. Potassium hexafluorophosphate (2 molar excess) in water is added and the solution is allowed to cool. The crystals which form are collected by filtration and dried in air to afford bis(4-isopropylphenyl)iodosyl hexafluorophosphate (0.4 g) m.pt. 84° C. Spectroscopic analysis shows:
Reaction SMILES: Cl[C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[C:4]([CH2:17][OH:18])[CH:3]=1.C(C1C=C(C=CC=1O)[C:24]#[N:25])=O>>[C:24]([C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[C:4]([CH:17]=[O:18])[CH:3]=1)#[N:25]
Reactant: N#Cc1ccc(O)c(C=O)c1
Reactant: CC(C)(C)OC(=O)COc1ccc(Cl)cc1CO
Product: CC(C)(C)OC(=O)COc1ccc(C#N)cc1C=O

Procedure:
Prepared by the method of example 1 part (d) using 3-formyl-4-hydroxy-benzonitrile to give the title compound (1.4 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH:16](O)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][CH:25]([C:28]2[CH:29]=[C:30]([NH:34][C:35](=[O:39])[CH:36]([CH3:38])[CH3:37])[CH:31]=[CH:32][CH:33]=2)[CH2:24][CH2:23]1.Cl>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:16]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[F:9])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]2[CH2:23][CH2:24][CH:25]([C:28]3[CH:29]=[C:30]([NH:34][C:35](=[O:39])[CH:36]([CH3:38])[CH3:37])[CH:31]=[CH:32][CH:33]=3)[CH2:26][CH2:27]2)=[CH:4][CH:3]=1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCCC(O)c3ccccc3F)CC2)c1
Reactant: Oc1ccc(F)cc1
Agent: Cl
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCCCC(Oc3ccc(F)cc3)c3ccccc3F)CC2)c1

Procedure:
Prepared by Procedure A and Scheme AN using 4-fluorophenol and N-(3-{1-[6-(2-fluorophenyl)-6-hydroxyhexyl]-4-piperidinyl}phenyl)-2-methylpropanamide: 1H NMR (400 MHz, CDCl3), HCl salt δ 7.72–6.72 (m, 12H), 5.42–5.34 (m, 1H), 3.68–3.58 (m, br, 2H), 3.02–2.92 (m, 2H), 2.802.46 (m, 6H), 2.05–1.78 (m, 6H), 1.68–1.56 (m, 1H), 1.56–1.38 (m, 3H), 1.25 (d, 6H, J=6.8 Hz); ESMS m/e: 535.1 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:25][C@H:26]4[CH2:31][CH2:30][C@H:29]([CH3:32])[CH2:28][CH2:27]4)[C:15]([C:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH2:18])=[N:16][C:12]=3[CH:11]=[C:10]([C:33]3[NH:37][C:36](=[O:38])[O:35][N:34]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1.[CH3:39][O-:40].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:25][C@H:26]4[CH2:27][CH2:28][C@H:29]([CH3:32])[CH2:30][CH2:31]4)[C:15]([CH:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:18][O:40][CH3:39])=[N:16][C:12]=3[CH:11]=[C:10]([C:33]3[NH:37][C:36](=[O:38])[O:35][N:34]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1
Reactant: C=C(c1ccccc1)c1nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c2n1C[C@H]1CC[C@H](C)CC1
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COCC(c1ccccc1)c1nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c2n1C[C@H]1CC[C@H](C)CC1
Temperature: 75 °C

Procedure:
3-[4-(5-Chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-(1-phenylethenyl)-3H-imidazo[4,5-c]pyridin-6-yl]-1,2,4-oxadiazol-5(4H)-one (Example 9.1, 130 mg, 0.247 mmol) was taken up in methanol (1.644 mL) at room temperature, and sodium methoxide (1.2 mL of 25 wt % in methanol, 5.25 mmol) was added. The mixture was capped and heated to 75° C. for 24 hours. The mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride, and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified via automated reverse phase HPLC (methanol/water+0.1% TFA modifier) to afford 3-{4-(5-chloropyridin-3-yl)-2-(2-methoxy-1-phenylethyl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one (TFA salt) as a white solid. MS ESI calcd. for C30H31ClN6O3 [M+H]+ 559. found 559. 1H NMR (500 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.83 (s, 2H), 8.40 (s, 1H), 8.32 (s, 1H), 7.58-7.48 (m, 2H), 7.31-7.25 (m, 3H), 4.80-4.75 (m, 1H), 4.21-4.15 (m, 1H), 3.90-3.80 (m, 3H), 3.25 (s, 3H), 1.42-1.35 (m, 1H), 1.29-1.20 (m, 2H), 1.04-0.94 (m, 1H), 0.75-0.64 (m, 5H), 0.40-0.29 (m, 4H).
Reaction SMILES: Cl[C:2]1([C:9]([O:11][CH3:12])=[O:10])[C:6](=[O:7])[C:5]([Cl:8])=[CH:4][S:3]1.[CH3:13][OH:14]>>[Cl:8][C:5]1[C:6]([OH:7])=[C:2]([C:9]([O:11][CH3:12])=[O:10])[S:3][C:4]=1[O:14][CH3:13]
Reactant: CO
Reactant: COC(=O)C1(Cl)SC=C(Cl)C1=O
Product: COC(=O)c1sc(OC)c(Cl)c1O

Procedure:
2,4-Dichloro-2-methoxycarbonylthiophene-3(2H)-one (10 mmol) was stirred in anhydrous methanol at room temperature for 4 hours and the precipitate filtered, m.p. 109°-111° C. (methanol).
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[CH:4]([CH:5]=[C:6]([Cl:8])[Cl:7])[CH:3]1[C:9](Cl)=[O:10].C(N(CC)CC)C.CC[O:22]CC>>[Cl:7][C:6]([Cl:8])=[CH:5][CH:4]1[CH:3]([C:9]([OH:22])=[O:10])[C:2]1([CH3:12])[CH3:1]
Reactant: CC1(C)C(C=C(Cl)Cl)C1C(=O)Cl
Reactant: CCOCC
Solvent: CCN(CC)CC
Product: CC1(C)C(C=C(Cl)Cl)C1C(=O)O
Temperature: 25 °C

Procedure:
To a cooled solution (10°-15° C.) of 2.0 grams (0.009 mole) of cyano(6-phenoxy-2-pyridine)methanol and 2.0 grams (0.009 mole) of 2,2-dimethyl-3-(2,2-dichloroethenyl)cyclopropane carboxylic acid chloride in 25 milliliters of anhydrous ether was added 1 milliliter of triethylamine. A white precipitate separated out immediately. The reaction mixture was stirred at room temperature for one-half (1/2) hour. The mixture was diluted with 50 milliliters of water and extracted thoroughly with ether. The ether extract was washed with water, dried over anhydrous magnesium sulfate and concentrated under vacuo to give 3.4 grams of crude 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylic acid:cyano(6-phenoxy-2-pyridinyl)methyl ester product as a thick brown oil. This oil was purified by distillation under reduced pressure to give 1.8 grams of a light brown oil boiling at 190°-200° C. at 0.1-0.2 milliliters of mercury (mm). The oil had a refractive index of n(25/D)=1.5264. The structure of the product was confirmed by its nuclear magnetic resonance spectrum (NMR). Upon analysis, the product was found to have carbon, hydrogen and nitrogen contents of 60.28, 4.47 and 6.62 percent, respectively, as compared with the theoretical contents of 60.44, 4.35 and 6.71 percent respectively, as calculated for the above compound. (Compound No. 1).
Reaction SMILES: [Cl:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([OH:11])[CH:8]=[CH:7][C:5]=2[N:6]=1.[CH:12](O)([CH3:14])[CH3:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][CH:12]([CH3:14])[CH3:13])[CH:8]=[CH:7][C:5]=2[N:6]=1
Reactant: CC(C)O
Reactant: Oc1ccc2nc(Cl)sc2c1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)Oc1ccc2nc(Cl)sc2c1
Reaction time: 1 h
Yield: 91.1 %

Procedure:
2-Chlorobenzo[d]thiazol-6-ol (0.800 g, 4.31 mmol), isopropanol (0.36 mL, 4.74 mmol) and triphenylphosphine (1.24 g, 4.74 mmol) were mixed in THF (1.4 mL) and sonicated. DIAD (0.933 mL, 4.74 mmol) was added dropwise over ˜2 min. After 1 h, the reaction mixture was concentrated under reduced pressure. The material was purified by column chromatography (0 to 10% EtOAc in Hexanes gradient), yielding 0.894 g (91%) of the title compound as a light brown oil. LC-MS: RT=10.21 min., [M+H]+=228.0. Rf=0.50 in 10% EtOAc/Hexanes.
Reaction SMILES: [N:1]1([C:6]([O:8][C:9]2[C:10]([F:20])=[CH:11][C:12]3[O:17][CH2:16][C:15](=[O:18])[NH:14][C:13]=3[CH:19]=2)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.I[CH2:22][CH2:23][CH3:24].C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CC(C)=O>[N:1]1([C:6]([O:8][C:9]2[C:10]([F:20])=[CH:11][C:12]3[O:17][CH2:16][C:15](=[O:18])[N:14]([CH2:22][CH2:23][CH3:24])[C:13]=3[CH:19]=2)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCCI
Reactant: O=C1COc2cc(F)c(OC(=O)N3CCCC3)cc2N1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCN1C(=O)COc2cc(F)c(OC(=O)N3CCCC3)cc21
Yield: 74.5 %

Procedure:
A stirred mixture of 0.70 g (0.0025 mole) of 7-fluoro-2H-1,4-benzoxazin-3(4H)-one-6-yl 1-pyrrolidinecarboxylate, 0.60 g (0.0036 mole) of 1-iodopropane, 1.1 g (0.0076 mole) of potassium carbonate, and 0.1 g (0.00038 mole) of 18-crown-6 in 50 mL of acetone was heated at reflux for five hours. The reaction mixture was cooled, filtered and the filtrate evaporated under reduced pressure leaving a residue. The residue was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated under reduced pressure leaving a residue. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate-heptane (50:50), to yield 0.6 g of (7-fluoro-4-propyl-2H-1,4-benzoxazin-3(4H)-one-6-yl) 1-pyrrolidinecarboxylate as a solid 73°-75° C., Compound 4 of Table 1. The nmr ir spectra were consistent with the proposed structure.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:17]=1.[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[BH4-].[Na+]>>[CH2:20]([N:14]1[CH2:13][CH:12]=[C:11]([C:9]2[S:10][C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:18])([F:1])[F:19])=[CH:17][C:7]=3[N:8]=2)[CH2:16][CH2:15]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: FC(F)(F)c1ccc2sc(-c3ccncc3)nc2c1
Reactant: BrCc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Product: FC(F)(F)c1ccc2sc(C3=CCN(Cc4ccccc4)CC3)nc2c1
Yield: 46.7 %

Procedure:
4-(5-Trifluoromethylbenzothiazol-2-yl)pyridine (10 g, 0.04 mol) was reacted with benzyl bromide (6.4 ml, 0.06 mol) followed by sodium borohydride (1.76 g, 0.052 mol) as exemplified in Example 7 step 2. The crude product was purified by flash chromatography eluting with 15% ethyl acetate in petroleum ether to give a yellow solid. Recrystallisation from ethyl acetate afforded the title compound as a pale yellow solid (7 g, 47%); mp. 124°-125° C.; (Found: C, 63.85; H, 4.48; N, 7.48. C20 H17F3N2S requires C, 64.16; H, 4.58; N, 7.48%). δH (CDCl3), 2.75 (2H, m, NCH2CH2), 2.81 (2H, m, NCH2CH2), 3.24 (2H, m, NCH2CH2), 3.67 (2H, s, NCH2Ar), 6.71 (1H, m, NCH2CH), 7.28 (5H, m, ArH), 7.55 (1H, d of d, J 8.4Hz, J 1.4Hz, ArH), 7.89 (1H, d, J 8.4Hz, ArH), 8.23 (1H, s, ArH); m/z (ES+) 375 (M+1)+.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.Cl.[NH2:13][C:14]([NH:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][NH:25][C:26](=[O:39])[C@@H:27]([CH2:29][CH2:30][CH2:31][NH:32][C:33]([NH2:38])=[N:34][N+:35]([O-:37])=[O:36])[NH2:28])=[CH:20][CH:19]=1)=[O:15].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[NH2:13][C:14]([NH:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:24][NH:25][C:26](=[O:39])[C@@H:27]([CH2:29][CH2:30][CH2:31][NH:32][C:33]([NH2:38])=[N:34][N+:35]([O-:37])=[O:36])[NH:28][C:9](=[O:11])[CH2:8][C:5]2[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=2)=[CH:22][CH:23]=1)=[O:15]
Reactant: NC(=O)NCc1ccc(CNC(=O)[C@H](N)CCCNC(N)=N[N+](=O)[O-])cc1
Reactant: O=C(O)Cc1ccc(O)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Product: NC(=O)NCc1ccc(CNC(=O)[C@@H](CCCNC(N)=N[N+](=O)[O-])NC(=O)Cc2ccc(O)cc2)cc1
Yield: 90 %

Procedure:
Prepared analogously to Example 14c) from 4-hydroxybenzene acetic acid, (R)-N-[[4-(aminocarbonylaminomethyl)phenyl]methyl]-N5 -[amino(nitroimino)methyl]-ornithinamidehydrochloride and TBTU in a yield of 90% of theory. Colourless crystals, Mp. 168-170° C.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[Cl-].[CH3:11][C:12]1[NH:16][C:15]([CH3:17])=[CH:14][NH+:13]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:11][C:12]1[N:13]([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)[CH:14]=[C:15]([CH3:17])[N:16]=1
Reactant: N#Cc1ccc(F)cc1
Reactant: Cc1c[nH+]c(C)[nH]1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cn(-c2ccc(C#N)cc2)c(C)n1
Temperature: 145 °C
Yield: 52.7 %

Procedure:
A mixture of 4-fluorobenzonitrile (3 g, 25 mmol), 2,4-dimethylimidazolium chloride (3 g, 25 mmol) and potassium carbonate (7.2 g, 52 mmol) in dimethylformamide (50 ml) was heated at 145° C. for 16 hours. Most of the solvent was evaporated in vacuo and the residue was partitioned between ethyl acetate and brine. The organic layer was driied (magnesium sulphate) and evaporated a yellow solid. Crystallization from hexane/ether afforded a pale-yellow solid (2.6 g, 57%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:7][CH2:8][O:9][C:10](Cl)=[O:11]>CCCCCC.C(OCC)(=O)C>[Cl:7][CH2:8][O:9][C:10]([N:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:11]
Reactant: C1CCNCC1
Reactant: O=C(Cl)OCCl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: O=C(OCCl)N1CCCCC1
Reaction time: 0.5 h
Yield: 89.6 %

Procedure:
Piperidine(1.06 g, 12.5 mmol) was added to a solution of chloroformic acid chloromethyl ester(645 mg, 5 mmol) in n-hexane (15 mL) at 0° C. under argon atmosphere, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate. After the ethyl acetate solution was washed successively with 1N hydrochloric acid(20 mL), water and brine, dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure to give the title compound(796 mg, 89.6%) as a colorless oil.
Reaction SMILES: [CH2:1]([N:5]1[C:9]([CH:10]=[O:11])=[CH:8][N:7]=[C:6]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].[CH2:18](OCC)C>>[CH2:1]([N:5]1[C:9]([CH:10]([OH:11])[CH3:18])=[CH:8][N:7]=[C:6]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCOCC
Reactant: CCCCn1c(C=O)cnc1-c1ccccc1
Product: CCCCn1c(C(C)O)cnc1-c1ccccc1

Procedure:
A solution of aldehyde 102 (230 mg) in diethyl ether (30 mL) is placed in a separatory funnel and treated with a solution of