Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O1CCCC1.B.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15](O)=[O:16])=[C:10]([I:18])[CH:9]=1.CO>O1CCCC1>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][OH:16])=[C:10]([I:18])[CH:9]=1
Reactant: O=C(O)Cc1ccc(Cl)cc1I
Agent: B
Solvent: C1CCOC1
Solvent: CO
Product: OCCc1ccc(Cl)cc1I
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 52.73 mmol of borane tetrahydrofuran complex (1N in tetrahydrofuran) is added dropwise to a stirred solution of 21.09 mmol of (4-chloro-2-iodo-phenyl)-acetic acid in 150 ml of dry tetrahydrofuran. The reaction mixture is stirred at room temperature for 1 hour then 20 ml of methanol are carefully added. The mixture is refluxed at 60° C. for 45 minutes, and then evaporated to dryness. The resulting residue is purified by flash chromatography (SiO2 60 F) to afford the title product as a yellowish solid. Rf=0.13 (EtOAc-heptane=1:4); Rt=4.27 (gradient I).
Reaction SMILES: Cl[C:2]1[C:3]2[CH2:12][CH2:11][CH2:10][O:9][C:4]=2[N:5]=[C:6]([NH2:8])[N:7]=1.[CH3:13][O-:14].[Na+]>CO>[CH3:13][O:14][C:2]1[C:3]2[CH2:12][CH2:11][CH2:10][O:9][C:4]=2[N:5]=[C:6]([NH2:8])[N:7]=1
Reactant: C[O-]
Reactant: Nc1nc(Cl)c2c(n1)OCCC2
Agent: [Na+]
Solvent: CO
Product: COc1nc(N)nc2c1CCCO2

Procedure:
6,7-Dihydro-4-hydroxy-5H-pyrano[2,3-d]pyrimidin-2-amine can be prepared from diethyl 3-chloropropylmalonate, guanidine carbonate and sodium ethoxide in ethanol. Treatment of the product ##STR56## with phosphorus oxychloride gives 4-chloro-6,7-dihydro-5H-pyrano[2,3-d]pyrimidin-2-amine and subsequent reaction with sodium methoxide in refluxing methanol affords 6,7-dihydro-4-methoxy-5H-pyrano[2,3-d]pyrimidin-2-amine.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:30])[C:17](=O)[C:16]3[C:15]([C:19](OCC)=[O:20])=[CH:14][CH:13]=[CH:12][C:11]=3[NH:10][CH:9]2[C:24]2[N:25]([CH3:29])[CH:26]=[CH:27][N:28]=2)=[CH:4][CH:3]=1.O.[NH2:32][NH2:33]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([OH:30])[C:17]3=[N:32][NH:33][C:19](=[O:20])[C:15]4[CH:14]=[CH:13][CH:12]=[C:11]([C:16]=43)[NH:10][CH:9]2[C:24]2[N:25]([CH3:29])[CH:26]=[CH:27][N:28]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cccc2c1C(=O)C(O)(c1ccc(F)cc1)C(c1nccn1C)N2
Reactant: NN
Solvent: O
Solvent: CO
Product: Cn1ccnc1C1Nc2cccc3c(=O)[nH]nc(c23)C1(O)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 80 %

Procedure:
A mixture of ethyl 3-(4-fluorophenyl)-3-hydroxy-2-(1-methyl-1H-imidazol-2-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (60 mg) in 85% hydrazine monohydrate (0.2 mL) and methanol (2 mL) was stirred at room temperature for 1 hr. Then the solvent was removed under reduced pressure. The residue was purified by prep-TLC (methanol:dichloromethane=1:20) to give the title compound (50 mg, yield 80%). LC-MS (ESI) m/z: 378 (M+1)+; 1H-NMR (400 MHz, DMSO-d6); 3.44 (s, 3H), 5.24 (s, 1H), 6.84 (s, 1H), 6.98-7.06 (m, 4H), 7.11-7.13 (d, J=8.0 Hz, 1H), 7.38-7.42 (m, 3H), 7.46 (s, 1H), 7.56-7.60 (t, J=8.0 Hz, 1H).
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:20])=[C:10]([N:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[C:11]=2[F:13])[C:6](=[O:21])[C:5]([C:22]([OH:24])=[O:23])=[CH:4]1)[CH3:2].[C:25]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1)(=[O:27])[CH3:26]>N1C=CC=CC=1.C1C=CC=CC=1>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:20])=[C:10]([N:14]3[CH2:15][CH2:16][N:17]([S:35]([C:32]4[CH:31]=[CH:30][C:29]([NH:28][C:25](=[O:27])[CH3:26])=[CH:34][CH:33]=4)(=[O:37])=[O:36])[CH2:18][CH2:19]3)[C:11]=2[F:13])[C:6](=[O:21])[C:5]([C:22]([OH:24])=[O:23])=[CH:4]1)[CH3:2]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCNCC3)c(F)c21
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: c1ccccc1
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(S(=O)(=O)c4ccc(NC(C)=O)cc4)CC3)c(F)c21
Reaction time: 1 h
Yield: 92.4 %

Procedure:
2.80 g of 1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid is suspended in 100 ml of pyridine. To this suspension is slowly added 7.76 g of 4-acetamidobenzenesulfonyl chloride in 20 ml of benzene under ice-cooling while stirring. Stirring is continued for 1 hour under ice-cooling and then for further 3 hours at room temperature. The reaction mixture is concentrated under reduced pressure. To the residue is added 1N sodium hydroxide solution to dissolve. The pH of the solution is then adjusted to 4 with acetic acid. Precipitating crystals are collected by filtration, washed with water and recrystallized from dimethylformamide (DMF)-ethanol to give 4.10 g of the titled compound. Melting point: 276°-277° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:36])[NH:7][CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[C:23]3[C:18](=[N:19][CH:20]=[CH:21][N:22]=3)[CH:17]=[C:16]([C:24]3[CH:29]=[CH:28][C:27]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[CH:26][CH:25]=3)[N:15]=2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:39]I>C1COCC1>[CH3:39][N:7]([CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[C:23]3[C:18](=[N:19][CH:20]=[CH:21][N:22]=3)[CH:17]=[C:16]([C:24]3[CH:29]=[CH:28][C:27]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[CH:26][CH:25]=3)[N:15]=2)[CH2:10]1)[C:6](=[O:36])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3]
Reactant: CI
Reactant: CC(C)(C)OC(=O)NC[C@@H]1CCN(c2nc(-c3ccc(N4CCOCC4)cc3)cc3nccnc23)C1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CN(C[C@@H]1CCN(c2nc(-c3ccc(N4CCOCC4)cc3)cc3nccnc23)C1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Under N2, to a solution of (S)-tert-butyl(1-(7-(4-morpholinophenyl)pyrido[4,3-b]pyrazin-5-yl)pyrrolidin-3-yl)methylcarbamate (150 mg, 0.31 mmol) in anhydrous THF (10 mL) was slowly added sodium hydride (49 mg, 1.22 mmol) at 0° C. The mixture was warmed up and stirred at room temperature for 0.5 h. The reaction mixture was then cooled to 0° C., and CH3I (174 mg, 1.22 mmol) was added slowly. After the completion of the addition, the reaction mixture was stirred at reflux for 4 hours, cooled to ambient temperature, quenched with H2O, and extracted with EtOAc. The combined extracts were dried and concentrated to give the title compound. MS (m/z): 505 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:3]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.Cl[C:20]1[CH:21]=[CH:22]C2N=C(N)N=C(N3C=NC=N3)C=2N=1>>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[CH:9]=[CH:8][C:4]3[N:5]=[CH:6][N:7]=[C:2]([CH2:20][CH2:21][CH3:22])[C:3]=3[N:11]=2)=[CH:13][CH:14]=1
Reactant: Fc1ccc(-c2ccc3ncnc(Cl)c3n2)cc1
Reactant: Nc1nc(-n2cncn2)c2nc(Cl)ccc2n1
Product: CCCc1ncnc2ccc(-c3ccc(F)cc3)nc12

Procedure:
The procedure of example 2 was repeated, except for the use of 4-chloro-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine (the synthesis of which has been disclosed in WO2006/135993) instead of 6-chloro-4-[1,2,4]triazol-1-yl-pyrido[3,2-d]pyrimidin-2-yl-amine as a starting material. The resulting compound was characterised by its mass spectrum as follows: MS (m/z) 268.0 [M+H]+; HPLC Rt=5.13 minutes (Method A).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][N:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH2:16][CH2:15]1.C([O-])([O-])=O.[Cs+].[Cs+].[NH2:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:2]2[CH:3]=[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:14]2[CH2:15][CH2:16][N:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH2:18][CH2:19]2)=[CH:35][CH:34]=1
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(Br)cc23)CC1
Reactant: NCc1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1COCCO1
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4ccc(CN)cc4)cc23)CC1
Temperature: 160 °C
Yield: 30.9 %

Procedure:
To a solution of 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (30.0 mg, 0.072 mmol), Cs2CO3 (95 mg, 0.290 mmol) and [4-(aminomethyl)phenyl boronic acid (55 mg, 0.290 mmol) in dioxane/H2O (1.5 mL/0.5 mL) was bubbled argon for 5 minutes prior to addition of Pd(PPh3)4 (7.5 mg, 0.0072 mmol). The reaction mixture was heated in a microwave reactor (Smith synthesizer) for 20 minutes at 160° C. The solvent was evaporated, and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine (10 mL), dried over MgSO4, filtered, concentrated, and purified by reverse phase HPLC (water/CH3CN, 0.1% TFA 10-90%) to give the title compound (9.8 mg, 31%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[S:10][CH:11]=[C:12]([C:15]([CH3:17])=O)[C:13]=2[OH:14])[CH:5]=[CH:6][C:7]=1[Cl:8].[N:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][NH:26][C:27]([C:29]2[S:30][C:31]([C:34]([NH:36][NH2:37])=[O:35])=[CH:32][CH:33]=2)=[O:28])=[CH:20][CH:19]=1.O>CN(C)C=O>[N:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][NH:26][C:27]([C:29]2[S:30][C:31]([C:34]([NH:36][N:37]=[C:15]([C:12]3[C:13]([OH:14])=[C:9]([C:4]4[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=4)[S:10][CH:11]=3)[CH3:17])=[O:35])=[CH:32][CH:33]=2)=[O:28])=[CH:20][CH:19]=1
Reactant: CC(=O)c1csc(-c2ccc(Cl)c(Cl)c2)c1O
Reactant: NNC(=O)c1ccc(C(=O)NCCc2ccncc2)s1
Solvent: CN(C)C=O
Solvent: O
Product: CC(=NNC(=O)c1ccc(C(=O)NCCc2ccncc2)s1)c1csc(-c2ccc(Cl)c(Cl)c2)c1O
Reaction time: 5 h
Yield: 66 %

Procedure:
2-(3,4-Dichlorophenyl)-3-hydroxy-4-methylcarbonylthiophene (0.11 g, 0.38 mmol) and 5-hydrazinocarbonylthiophene-2-carboxylic acid (2-pyridin-4-yl)ethylamide (0.10 g, 0.34 mmol) prepared in Reference Synthetic Example 17 were suspended in N,N-dimethylformamide (2.0 mL) and left at 100° C. for 5 hours and then at room temperature for 20 hours. Water (0.20 mL) was added with stirring, and the precipitated solid was recovered by filtration, washed with chloroform and dried to give the desired product, 5-{1-[5-(3,4-dichlorophenyl)-4-hydroxythiophen-3-yl]ethylidenehydrazinocarbonyl}thiophene-2-carboxylic acid 2-(pyridin-4-yl)ethylamide (yield 66%).
Reaction SMILES: CCN(C(C)C)C(C)C.[C:10]1([N:16]2[CH:20]=[C:19]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[N:18]=[CH:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH:50]1[CH2:53][CH:52]([O:54][C:55]2[CH:56]=[C:57]([CH:60]=[CH:61][C:62]=2[CH3:63])[C:58]#[N:59])[CH2:51]1>CN(C=O)C>[C:58]([C:57]1[CH:60]=[CH:61][C:62]([CH3:63])=[C:55]([CH:56]=1)[O:54][CH:52]1[CH2:51][N:50]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:19]2[N:18]=[CH:17][N:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:20]=2)=[O:22])[CH2:53]1)#[N:59]
Reactant: O=C(O)CNC(=O)c1cn(-c2ccccc2)cn1
Reactant: Cc1ccc(C#N)cc1OC1CNC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(C#N)cc1OC1CN(C(=O)CNC(=O)c2cn(-c3ccccc3)cn2)C1
Reaction time: 0.03 h
Yield: 18.7 %

Procedure:
DIPEA (193.9 mg, 1.5 mmol) was added to a stirred solution of [(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid (prepared from Intermediate 68 by means of Step 3 of the General Scheme) (92 mg, 0.37 mmol) in DMF (3 mL) followed by HOBt (53.2 mg, 0.39 mmol) and EDCI (75.5 mg, 0.39 mmol). After 2 minutes of stirring, 3-(azetidin-3-yloxy)-4-methyl-benzonitrile hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (84 mg, 0.37 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. Partitioning with cold water and ethyl acetate and concentration of the organic layer after drying over sodium sulfate afforded a residue which was purified by preparative HPLC to afford 29 mg (18.7% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(5-cyano-2-methyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 416, 98.6%. 1H NMR (300 MHz, DMSO-d6): δ 8.38 (d, 1H), 8.28 (d, 1H), 8.12 (t, 1H), 7.7 (d, 2H), 7.5 (t, 2H), 7.38 (m, 3H), 7.16 (s, 1H), 5.2 (m, 1H), 4.7 (t, 1H), 4.4 (m, 1H), 4.2 (m, 1H), 3.8 (m, 3H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:24]=[CH:23][C:12]([O:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([C:20]([OH:22])=O)[CH:15]=3)=[CH:11][CH:10]=2)[CH:5]=[C:4]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:3]=1.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>>[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([C:20]([C:16]2[CH:15]=[C:14]([O:13][C:12]3[CH:11]=[CH:10][C:9]([NH:8][C:6]4[CH:5]=[C:4]([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:3]=[C:2]([NH2:1])[N:7]=4)=[CH:24][CH:23]=3)[CH:19]=[CH:18][N:17]=2)=[O:22])[CH2:34][CH2:33]1
Reactant: CN1CCNCC1
Reactant: Nc1nc(Nc2ccc(Oc3ccnc(C(=O)O)c3)cc2)cc(-c2ccccc2)n1
Product: CN1CCN(C(=O)c2cc(Oc3ccc(Nc4cc(-c5ccccc5)nc(N)n4)cc3)ccn2)CC1

Procedure:
This material is prepared by a method analogous to that described for Example 21, starting from 4-{4-[(2-amino-6-phenylpyrimidin-4-yl)amino]phenoxy}pyridine-2-carboxylic acid (Example 20) and 1-methylpiperizine. 1H NMR (DMSO-d6) δ 10.85 (s, 1H), 10.19 (s, 1H), 8.42 (d, 1H), 7.90 (m, 2H), 7.74 (m, 3H), 7.59 (m, 4H), 7.22 (m, 3H), 7.06 (m, 2H), 6.60 (s,1H), 4.51 (m, 1H), 4.08 (m, 1H), 3.45 (m, 3H), 3.17 (m, 3H), 2.78 (s, 3H); MS ES 482 (M+H)+, calcd 482, RT=1.86 min.
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]2([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=[CH:4][N:3]=1.Cl[CH:20]([C:26]([CH3:28])=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22]>CO.C(OCC)(=O)C>[CH3:28][C:26]1[N:1]=[C:2]2[C:7]([O:8][CH2:9][C:10]3([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH2:12][CH2:11]3)=[CH:6][CH:5]=[CH:4][N:3]2[C:20]=1[C:21]([O:23][CH2:24][CH3:25])=[O:22]
Reactant: CCOC(=O)C(Cl)C(C)=O
Reactant: Nc1ncccc1OCC1(c2ccccc2)CC1
Solvent: CO
Solvent: CCOC(C)=O
Product: CCOC(=O)c1c(C)nc2c(OCC3(c4ccccc4)CC3)cccn12
Yield: 8.6 %

Procedure:
A stirred mixture of 2-amino-3-[(1-phenylcyclopropyl)methoxy]pyridine (2.82 g, 11.7 mmol, see example 23), ethyl 2-chloroacetoacetate (6.5 mL, 47 mmol) and molecular sieves (15.1 g, type 4 Å, beads, 8–12 mesh) in anhydrous methanol (55 mL) was refluxed for 39 h under argon. The molecular sieves were filtered off and the filtrate was concentrated in vacuo to give an oil which was dissolved in ethyl acetate (200 mL) and then washed successively with a 1:1 (v/v) mixture of saturated aq sodium bicarbonate and water (2×25 mL), and water (20 mL). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo to yield the crude product. Purification by dry column (600 mL funnel with 450 mL of silica gel 10–40μ, Sigma cat. S-6628) eluted with a mixture of ethyl acetate-hexanes (1:3 v/v, containing 0.5% v/v isopropylarnine) afforded 0.352 g (8.6% yield) of ethyl 2-methyl-8-[(1-phenylcyclopropyl)methoxy]imidazo[1,2-α]pyridine-3-carboxylate (Rf=0.30 in ethyl acetate-hexanes, 1:3 v/v, containing 0.5% v/v isopropylamine). A stirred solution of ethyl 2-methyl-8-[(1-phenylcyclopropyl)methoxy]imidazo[1,2-α]pyridine-3-carboxylate (0.190 g, 0.542 mmol) in a mixture of dichloromethane (3.5 mL) and anhydrous diethyl ether (3 mL) was treated with ethereal hydrogen chloride to form the hydrochloride salt. Concentration of the solution in vacuo gave a residue which was triturated in anhydrous diethyl ether to afford the title compound as an off-white solid (0.168 g, 80% yield). 1H-NMR (300 MHz, CDCl3) δ 16.91 (br s, 1H, +NH), 9.05 (d, 1H, Ar), 7.65 (d, 2H, Ar), 7.18 (m, 4H, Ar), 6.92 (d, 1H, Ar), 4.45 (q, 2H, CH3CH2), 4.32 (s, 2H, CH2O), 3.03 (s, 3H, CH3), 1.42 (t, 3H, CH3CH2), 1.15 (m, 4H, CH2CH2); 13C-NMR (75 MHz, CDCl3, APT) δ 159.49 (+), 145.10 (+), 143.90 (+), 142.24 (+), 133.68 (+), 130.21 (−), 128.26 (−), 126.78 (−), 120.27 (−), 118.13 (−), 113.77 (+), 112.02 (−), 78.61 (+), 62.09 (+), 25.48 (+), 14.14 (−), 12.56 (−), 11.51 (+); LRMS-FAB m/z: MH+ 351 (100%); Anal. calcd for C21H22N2O3.HCl: C, 65.20; H, 5.99; N, 7.24%. found: C, 64.87; H, 5.96; N, 7.20%.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[OH:32][C@@H:33]([CH3:41])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].[NH2:42][C:43]1[N:48]=[CH:47][C:46]([C:49]2[CH:54]=[CH:53][C:52](O)=[C:51]([F:56])[CH:50]=2)=[CH:45][N:44]=1>O1CCCC1>[NH2:42][C:43]1[N:48]=[CH:47][C:46]([C:49]2[CH:54]=[CH:53][C:52]([O:32][CH:33]([CH3:41])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[C:51]([F:56])[CH:50]=2)=[CH:45][N:44]=1
Reactant: C[C@H](O)C(=O)OC(C)(C)C
Reactant: Nc1ncc(-c2ccc(O)c(F)c2)cn1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(Oc1ccc(-c2cnc(N)nc2)cc1F)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 72 %

Procedure:
To a solution of triphenylphosphine (0.315 g, 1.2 mmol) in tetrahydrofuran (THF, 5.0 mL) was added diethyl azodicarboxylate (0.19 mL, 1.2 mmol) and tert-butyl (S)-2-hydroxypropanoate (292 mg, 2 mmol) followed by 4-(2-aminopyrimidin-5-yl)-2-fluorophenol (0.20 g, 1.0 mmol) at RT (RT) under nitrogen. The mixture was stirred overnight at RT, evaporated and the residue was purified by chromatography on silica gel to afford the desired product (0.24 g, 72%). LCMS: (M+H)=334.1.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[OH:12].[Br:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N:20]=[C:21]=[O:22]>>[OH:12][C:3]1[CH:4]=[CH:5][C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]=1[NH:1][C:21]([NH:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[Br:13])=[O:22]
Reactant: O=C=Nc1ccccc1Br
Reactant: Nc1c(O)ccc2ccccc12
Product: O=C(Nc1ccccc1Br)Nc1c(O)ccc2ccccc12
Yield: 8.4 %

Procedure:
The urea was prepared from 1-amino 2-hydroxy napthalene(195 mg, 1 mmol) and 2-bromo phenyl isocyanate(1 mmol) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the title compound(0.030 g, 8%). EI-MS m/z 357(M+H)+
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[Al](C)C.CO[C:13]([C:15]1[CH:16]=[C:17]([NH2:30])[C:18]2[N:19]([N:21]=[C:22]([C:24]3[O:25][C:26]([Br:29])=[CH:27][CH:28]=3)[N:23]=2)[CH:20]=1)=[O:14].Cl>O1CCOCC1.C1(C)C=CC=CC=1>[NH2:30][C:17]1[C:18]2[N:19]([N:21]=[C:22]([C:24]3[O:25][C:26]([Br:29])=[CH:27][CH:28]=3)[N:23]=2)[CH:20]=[C:15]([C:13]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:14])[CH:16]=1
Reactant: COC(=O)c1cc(N)c2nc(-c3ccc(Br)o3)nn2c1
Reactant: C1CCNCC1
Agent: C[Al](C)C
Agent: Cl
Solvent: Cc1ccccc1
Solvent: C1COCCO1
Product: Nc1cc(C(=O)N2CCCCC2)cn2nc(-c3ccc(Br)o3)nc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 29.9 %

Procedure:
A solution of 20 mg (0.24 mmol) piperidine in 1 ml dioxane was treated with 0.24 ml (0.24 mmol) trimethylaluminum in toluene and stirred for 1 h at room temperature. 20 mg (0.06 mmol) 8-Amino-2-(5-bromo-furan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-6-carboxylic acid methyl ester in 1 ml dioxane was added and the mixture was heated to 90° C. for 72 h. 0.5 ml 1N HCl aq. was added and the volatiles were removed. The residue was taken up in 1.5 ml formic acid and 0.5 ml methanol and purified by reversed phase preparative HPLC eluting with a gradient of acetonitrile and water. The elution solvents were evaporated to obtain 7 mg (29%) of the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][CH2:15][CH3:16])=[C:6]([C:17](O)=[O:18])[C:5]=1[C:20](O)=[O:21])[CH3:2].[NH2:23][C:24]1[CH:34]=[CH:33][C:27]([CH2:28][S:29]([NH2:32])(=[O:31])=[O:30])=[CH:26][CH:25]=1.O>C(O)(=O)C>[CH2:15]([O:14][C:7]1[C:6]2[C:17](=[O:18])[N:23]([C:24]3[CH:34]=[CH:33][C:27]([CH2:28][S:29]([NH2:32])(=[O:30])=[O:31])=[CH:26][CH:25]=3)[C:20](=[O:21])[C:5]=2[C:4]([O:3][CH2:1][CH3:2])=[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=12)[CH3:16]
Reactant: CCOc1c(C(=O)O)c(C(=O)O)c(OCC)c2ccccc12
Reactant: Nc1ccc(CS(N)(=O)=O)cc1
Solvent: O
Solvent: CC(=O)O
Product: CCOc1c2c(c(OCC)c3ccccc13)C(=O)N(c1ccc(CS(N)(=O)=O)cc1)C2=O
Temperature: 120 °C
Yield: 75.6 %

Procedure:
To a solution of 1,4-diethoxy-2,3-naphthalenedicarboxylic acid (0.75 g, 2.5 mmol, 1.1 eqs) in glacial acetic acid (5 ml) was added 4-amino-benzylsulfonamide (0.43 g, 2.3 mmol). The reaction mixture was heated at 120° C. for 18 h. The reaction mixture was allowed to cool to ambient temperature and then poured into water (5 ml). The precipitate was filtered off, triturated with ethyl acetate/40:60 petroleum ether and then dried in vacuo to give the title compound as a beige solid (790 mg, 69%). δH [2H6]—DMSO 1.48 (6H, t); 4.40 (2H, s); 4.52 (4H, q); 7.00 (2H, s); 7.51 (2H, d, 8.5Hz); 7.56 (2H, d, 8.5 Hz); 7.89 (2H, m); 8.43 (2H, m)
Reaction SMILES: Cl[CH2:2]/[CH:3]=[CH:4]/[CH2:5][CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.[I-:12].[Na+].CCCCCC>CC(C)=O>[CH:6]1([CH2:5]/[CH:4]=[CH:3]/[CH2:2][I:12])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1
Reactant: [I-]
Reactant: ClC/C=C/CC1CCCCC1
Agent: [Na+]
Solvent: CCCCCC
Solvent: CC(C)=O
Product: IC/C=C/CC1CCCCC1
Reaction time: 8 h
Yield: 76 %

Procedure:
The chloride (B) (38.6 g) was added to a solution of sodium iodide (55.7 g) in acetone (1 litre) and the solution was allowed to stand overnight. Hexane (500 ml) was added and the precipitated solid was removed by filtration. The filtrate was concentrated and the residue partitioned between water (500 ml) and hexane (500 ml). The organic phase was separated, washed with saturated sodium thiosulphate solution (500 ml) and saturated sodium chloride solution (2×500 ml), and dried (MgSO4). The solvent was removed by evaporation and the residual liquid distilled under vacuum to give (2E)-4-cyclohexyl-1-iodobut-2-ene (C) as a dark liquid (44.9 g), b.p. 80°-85° C. at 0.15 mm Hg; NMR: 0.8-1.8(complex m, 11H), 1.9(t, 2H), 3.9(m, 2H), 5.7(m, 2H). (iii) A 1.6M solution of butyllithium in hexane (93.9 ml) was added dropwise over 30 minutes to a stirred solution of diisopropylamine (21.9 ml) in dry tetrahydrofuran (THF) (200 ml) at 0° C. under an atmosphere of argon. The temperature was maintained at 0° C. for 30 minutes and then the solution was cooled to -40° C. A solution of (4S)-4-benzyl-3-(3-methylbutyryl)oxazolidin-2-one (31.3 g) (obtained as described in Tetrahedron. 1987, 44, 5525) in dry THF (70 ml) was added dropwise over 30 minutes. The solution was kept at -40° C. for 30 minutes and then the temperature was allowed to rise to 0° C. A solution of iodide (C) (39.0 g) in dry THF (75 ml) was added dropwise over 30 minutes, and then the solution was stirred at 0° C. for 1 hour. Saturated sodium chloride solution (250 ml) was added and the mixture was extracted with ether (3×250 ml). The extracts were washed with saturated sodium chloride solution (2×250 ml) and dried (MgSO4). The solvent was removed by evaporation and the residue was purified by flash chromatography, eluting with ethyl acetate/hexane (8:92 v/v), to give (4s)-4-benzyl-3-[(2S,4E)-6-cyclohexyl-2-isopropylhex-4-enoyl]oxazolidin-2-one (A) (34.5 g) as a clear oil; NMR: 0.8 -1.2(complex m, 12H), 1.6(m, 6H), 1.85(t, 1H), 2.0(m, 2H), 2.35(m, 2H), 2.6(m, 1H), 3.3(dt, 1H), 3.8(m, 1H), 4.1(d, 1H), 4.7(m, 1H), 5.4(m, 2H), 7.3(m, 5H); mass spectrum (+ve FAB), 398 (M+H+); 22 [α]436 +45.8 (c, 1.04, CHCl3). ##STR1##