Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([NH:6][C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:23][N:24]1CCC(N)CC1>>[CH3:13][C:12]1[C:7]([NH:6][CH:1]2[CH2:2][CH2:3][N:24]([CH3:23])[CH2:4][CH2:5]2)=[N:8][C:9]([NH:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[N:10][C:11]=1[CH3:14]
Reactant: CN1CCC(N)CC1
Reactant: Cc1nc(NCc2ccccn2)nc(NC2CCCC2)c1C
Product: Cc1nc(NCc2ccccn2)nc(NC2CCN(C)CC2)c1C

Procedure:
The titled compound was synthesized according to the procedure described for preparation of N4-cyclopentyl-5,6-dimethyl-N2-(pyridin-2-ylmethyl)pyrimidine-2,4-diamine (Example 29) using 1-methylpiperidin-4-amine instead of cyclopentanamine. The crude material was purified by column chromatography eluting with mixture of chloroform/ethanol/20% water solution of ammonia (200:10:1), and then the final product was washed with diethyl ether to afford the titled compound as a light-grey solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.68 (bs, 4H) 1.85 (s, 3H) 2.13 (bs, 3H) 2.57 (bs, 3H) 2.66 (bs, 2H) 3.13 (d, J=11.82 Hz, 2H) 3.81 (bs, 1H) 4.52 (d, J=5.91 Hz, 2H) 6.52 (s, 1H) 7.15-7.22 (m, 1H) 7.27 (d, J=7.79 Hz, 1H) 7.70 (d, J=7.66 Hz, 1H) 8.48 (d, J=4.03 Hz, 1H); MS (ESI) m/z 327.5 (M+1)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[S:16][CH:17]=[C:18]([C:20](OCC)=[O:21])[N:19]=2)([CH3:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([C:15]2[S:16][CH:17]=[C:18]([CH2:20][OH:21])[N:19]=2)([CH3:14])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCOC(=O)c1csc(C2(C)CCN(C(=O)OC(C)(C)C)CC2)n1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(C)(c2nc(CO)cs2)CC1
Reaction time: 2 h

Procedure:
To a solution of 4-(4-ethoxycarbonyl-thiazol-2-yl)-4-methyl-piperidine-1-carboxylic acid tert-butyl ester (0.6 g, 1.7 mmol) in anhydrous THF (10 mL) was added LiAlH4 (0.1 g, 2.6 mmol) at 0° C. The mixture was kept at 0° C. for 2 hours and the reaction was quenched with EtOH. The solvent was evaporated and the residue was diluted with EtOAc, washed with 1N NaOH, brine. After drying (Na2SO4), the solvent was removed in vacuo, and the residue was purified by silica column chromatography with EtOAc/hexanes to afford the desired product.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]1[CH2:18][C:10]2[S:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>O1CCOCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[CH:8][C:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[S:11][C:10]=2[CH:18]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1CCc2c(sc3ccccc23)C1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: C1COCCO1
Product: CCOC(=O)c1ccc2c(c1)sc1ccccc12

Procedure:
To a solution of 2.5 g. of 1,2,3,4-tetrahydrodibenzothiophene-3-carboxylic acid ethyl ester in 100 ml. of dioxane was added 4.7 g. of 2,3-dichloro-5,6dicyano-1,4-benzoquinone. The solution was stirred and refluxed for 31 hours. The solution was cooled and the hydroquinone filtered off. The dioxane was removed on a steam bath under reduced pressure. The residue was dissolved in 100 ml. of methylene chloride and the solution passed through a column containing about 75 g. of alumina (Woelm, grade 1). The solvent was removed on a steam bath and the residue crystallized from hexane. The yield of dibenzothiophene-3-carboxylic acid ethyl ester, m.p. 74°-78° was 1.7 g.
Reaction SMILES: [CH:1]1[C:4]2[CH:5]=[CH:6][C:7]([N:9]3[C:13](=[O:14])[C:12]4=[CH:15][C:16]([N+:19]([O-])=O)=[CH:17][CH:18]=[C:11]4[C:10]3=[O:22])=[CH:8][C:3]=2[CH:2]=1.[O-]S([O-])(=O)=O.[Mg+2].[K+].[Br-]>[Pd].C(OCC)(=O)C>[CH:1]1[C:4]2[CH:5]=[CH:6][C:7]([N:9]3[C:13](=[O:14])[C:12]4=[CH:15][C:16]([NH2:19])=[CH:17][CH:18]=[C:11]4[C:10]3=[O:22])=[CH:8][C:3]=2[CH:2]=1
Reactant: O=C1c2ccc([N+](=O)[O-])cc2C(=O)N1c1ccc2c(c1)C=C2
Agent: [Pd]
Agent: O=S(=O)([O-])[O-]
Agent: [Br-]
Solvent: CCOC(C)=O
Product: Nc1ccc2c(c1)C(=O)N(c1ccc3c(c1)C=C3)C2=O

Procedure:
1.50 g (5.10 mmol) of N-4 benzocyclobutenyl-4-nitrophthalimide, 1.70 g of MgSO4, 0.2 g of 10% Pd/C and 60 ml of ethyl acetate were placed in a pressure bottle and the mixture was then rocked on a hydrogenator under initial hydrogen pressure of 60 psi for about 17 hrs. The resultant reaction mixture, which was yellow-green, was filtered through celite and the solid residue was washed with acetone until the filtrate was colorless. The combined yellow-green filtrate was stripped to dryness to provide greenish yellow product, which was collected on a fritted filter funnel, washed with petroleum ether and dried in vacuo overnight. Yield: 1.20 g (88.9%). The product was used in the subsequent reaction without further purification. Mass Spectroscopy: M+ (264 100%). IR (KBr plate): ν(NH2):3290 m, 3390 m cm-1 ; ν(CH2) 2860 w, 2940 m; ν(imide): 1773 ms, 1690 vs cm-1, δ(imide) 744 ms, 1HNMR (acetone): 2.93 ppm (s, broad 2H); 3.23 ppm (5.4 H): 7.45 (center, complex, 6 H).
Reaction SMILES: N#N.[Br:3][C:4]1[CH:5]=[N:6][N:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:9][C:8]=12.CCN(C(C)C)C(C)C.Cl[C:29]([O:31][CH:32]([CH3:34])[CH3:33])=[O:30]>C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH:32]([O:31][C:29]([N:16]1[CH2:17][CH2:18][N:13]([C:10]2[CH:11]=[CH:12][N:7]3[N:6]=[CH:5][C:4]([Br:3])=[C:8]3[N:9]=2)[CH2:14][CH2:15]1)=[O:30])([CH3:34])[CH3:33]
Reactant: CC(C)OC(=O)Cl
Reactant: Brc1cnn2ccc(N3CCNCC3)nc12
Agent: N#N
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)OC(=O)N1CCN(c2ccn3ncc(Br)c3n2)CC1
Temperature: 0 °C

Procedure:
To a rapidly stirred, 0° C., N2 blanketed, solution of 3-bromo-5-piperazin-1-yl-pyrazolo[1,5-a]pyrimidine (15.8 g, 56.0 mmol) and Hunig's base [7087-68-5] (20.0 mL, 114.8 mmol) in ethyl acetate (280 mL) was steadily added a 1.0M solution of isopropyl chloroformate in toluene (67.0 mL) over the course of 10 minutes. The reaction was allowed to stir and warm to ambient temperature over night at which time it was washed with brine, dried (MgSO4), preloaded onto silica gel, chromatographed (Silica gel, eluted with 100% ethyl acetate) and crystallized from ethyl acetate/heptane to afford 13.2 g of white powder, mp. 78-79° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (d, J=6.32 Hz, 6 H) 3.44-3.54 (m, 4 H) 3.67-3.79 (m, 4 H) 4.82 (spt, J=6.23 Hz, 1 H) 6.77 (d, J=7.83 Hz, 1 H) 7.97 (s, 1 H) 8.69 (d, J=7.83 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6) δ ppm 21.94, 42.80, 43.87, 68.17, 77.32, 97.66, 136.47, 143.87, 144.40, 154.29, 155.64. LRMS (ESI) m/z 368.0/370.0 [(M+H)]+, calc'd for C14H18BrN5O2: 368.24.
Reaction SMILES: [C:1]([C:3]1[CH:23]=[CH:22][C:6]2[N:7]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([N:16]4[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]4)[CH:11]=3)[CH:8]=[N:9][C:5]=2[CH:4]=1)#[N:2].Cl.[OH:25]N.C(N(CC)CC)C>C(O)=O.O.[Ni]>[CH:1](=[N:2][OH:25])[C:3]1[CH:23]=[CH:22][C:6]2[N:7]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([N:16]4[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]4)[CH:11]=3)[CH:8]=[N:9][C:5]=2[CH:4]=1
Reactant: NO
Reactant: N#Cc1ccc2c(c1)ncn2-c1cccc(N2CCCCC2)c1
Agent: [Ni]
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: O=CO
Product: ON=Cc1ccc2c(c1)ncn2-c1cccc(N2CCCCC2)c1
Reaction time: 3 h
Yield: 69.9 %

Procedure:
To a solution of 3a1 (3.83 g, 12.9 mmol) in a mixture of formic acid (45 ml) and water (15 ml) was added Raney Ni (2.14 g, slurry in water). The mixture was refluxed with stirring for 3 hours. After cooling the mixture was filtered through celite and the filtrate was evaporated to dryness. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate (1M). The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The concentrate was eluted through a short silica gel is column with ethyl acetate. Evaporation of the solvent left 5-formyl-1-(3-(1-piperidinyl)phenyl)-benzimidazole (3.86 g, 100%) as an oil. This oil was dissolved in refluxing ethanol (15 ml). Hydroxyl amine hydrochloride (2.64 g, 38.0 mmol) and triethylamine (1.70 ml) was added and reflux was continued for 5 hours. The cooled mixture was rendered basic by addition of triethylamine. Water was added and the pricipitate was filtered off, washed with water and dried to yield 3b1 (2.89 g, 70%). M.p. 213-214° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]([CH3:15])[CH3:14])=[N:10][C:9]=2[C:16]2[C:17]([F:33])=[C:18]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[CH3:32])(=[O:25])=[O:24])[CH:19]=[CH:20][CH:21]=2)[CH:5]=[CH:4][N:3]=1.[CH2:34]([NH2:38])[CH:35]([CH3:37])[CH3:36]>>[F:33][C:17]1[C:16]([C:9]2[N:10]=[C:11]([CH:13]([CH3:15])[CH3:14])[S:12][C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:38][CH2:34][CH:35]([CH3:37])[CH3:36])[N:7]=2)=[CH:21][CH:20]=[CH:19][C:18]=1[NH:22][S:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH3:32])(=[O:25])=[O:24]
Reactant: Cc1ccccc1S(=O)(=O)Nc1cccc(-c2nc(C(C)C)sc2-c2ccnc(Cl)n2)c1F
Reactant: CC(C)CN
Product: Cc1ccccc1S(=O)(=O)Nc1cccc(-c2nc(C(C)C)sc2-c2ccnc(NCC(C)C)n2)c1F

Procedure:
Following a procedure analogous to the procedure described in Example 18, Step B using N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2-methylbenzenesulfonamide (70 mg, 0.139 mmol) and isobutylamine (0.140 mL, 1.39 mmol) the title compound was obtained as a light yellow solid (45 mg, 60% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.37 (s, 1H), 8.01 (d, J=5.1 Hz, 1H), 7.67-7.85 (m, 1H), 7.41-7.59 (m, 1H), 7.28-7.42 (m, 4H), 7.15-7.28 (m, 2H), 5.64-5.89 (m, 1H), 3.23-3.30 (m, 1H), 2.88-3.13 (m, 2H), 2.57 (s, 3H), 1.72-1.91 (m, 1H), 1.34 (d, J=6.8 Hz, 6H), 0.86 (d, J=6.1 Hz, 6H). MS (ESI): 540.0 [M+H]+.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[Cl:5][C:6]1[N:7]=[C:8]2[N:12]([CH:13]=1)[N:11]=[C:10]([CH2:14][O:15][CH3:16])[S:9]2.Cl[CH2:18][N:19]1[CH2:23][CH:22]([CH2:24][CH2:25][C:26]([F:29])([F:28])[F:27])[CH2:21][C:20]1=[O:30].C([O-])(O)=O.[Na+]>O1CCOCC1>[Cl:5][C:6]1[N:7]=[C:8]2[N:12]([C:13]=1[CH2:18][N:19]1[CH2:23][CH:22]([CH2:24][CH2:25][C:26]([F:29])([F:28])[F:27])[CH2:21][C:20]1=[O:30])[N:11]=[C:10]([CH2:14][O:15][CH3:16])[S:9]2
Reactant: O=C1CC(CCC(F)(F)F)CN1CCl
Reactant: COCc1nn2cc(Cl)nc2s1
Agent: O=C([O-])O
Agent: [Al+3]
Agent: [Cl-]
Solvent: C1COCCO1
Product: COCc1nn2c(CN3CC(CCC(F)(F)F)CC3=O)c(Cl)nc2s1
Temperature: 85 °C
Yield: 56 %

Procedure:
To a hot solution (80° C.) of AlCl3 (0.842 g, 6.3 mmol, 1 eq) and 6-chloro-2-(methoxy-methyl)imidazo[2,1-b][1,3,4]thiadiazole a35 (0.643 g, 3.156 mmol, 1 eq) in dioxane (35 ml) is added a solution of 1-(chloromethyl)-4-(3,3,3-trifluoropropyl)pyrrolidin-2-one a20 (1.2 g) in dioxane (5 ml). The reaction mixture is heated at 85° C. for 3 days. After cooling and hydrolysis by a saturated solution of NaHCO3 (40 ml), the crude reaction mixture is extracted by ethyl acetate (3×25 ml). The cumulated organic layers are dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified by chromatography over silicagel (eluent CH2Cl2/MeOH/NH4OH 99:1:0.1) and recrystallized from diisopropyl ether to afford pure (+)-1-{[6-chloro-2-(methoxymethyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(3,3,3-trifluoropropyl)pyrrolidin-2-one 27.
Reaction SMILES: [CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[O:33]1[C:37]2[CH:38]=[CH:39][C:40]([CH2:42][CH2:43][NH2:44])=[CH:41][C:36]=2[O:35][CH2:34]1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(C(C)C)CC)(C)C>O.C(=O)(O)[O-].[Na+].CN(C)C=O>[O:33]1[C:37]2[CH:38]=[CH:39][C:40]([CH2:42][CH2:43][NH:44][C:26](=[O:28])[C:25]3[CH:29]=[CH:30][C:22]([NH:21][C:19]4[N:18]=[CH:17][C:8]5[N:9]([CH3:16])[C:10](=[O:15])[C:11]([F:14])([F:13])[CH2:12][N:6]([CH:1]6[CH2:2][CH2:3][CH2:4][CH2:5]6)[C:7]=5[N:20]=4)=[C:23]([O:31][CH3:32])[CH:24]=3)=[CH:41][C:36]=2[O:35][CH2:34]1
Reactant: COc1cc(C(=O)O)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C
Reactant: NCCc1ccc2c(c1)OCO2
Agent: CN(C)C(N(C)C)=[N+]1N=[N+]([O-])c2ncccc21
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])O
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(C(=O)NCCc2ccc3c(c2)OCO3)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C
Reaction time: 18 h
Yield: 61.2 %

Procedure:
A mixture of 0.100 g (0.22 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-22), 0.069 g (0.42 mmole) of 2-benzo[1,3]dioxol-5-yl-ethylamine, 0.102 g (0.27 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.195 mL (1.12 mmole) of diisopropylethyl amine and 2.0 mL of dimethylformamide was stirred for 18 hours. The mixture was diluted with 10 mL of water plus 2 mL of saturated aqueous sodium bicarbonate and then extracted 3 times with 10 mL of ethyl acetate. The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with hexanes-ethyl acetate (gradient, 80:20-0:100) to give 0.080 g of N-(2-benzo[1,3]dioxol-5-yl-ethyl)-4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzamide (I-43) as a white solid.
Reaction SMILES: [C:1]([C:4]1[N:5]=[C:6]([F:28])[N:7]([C:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:8]=1)([OH:3])=[O:2].[CH2:29](I)[CH3:30].O>C1COCC1>[CH2:29]([O:2][C:1]([C:4]1[N:5]=[C:6]([F:28])[N:7]([C:9]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:8]=1)=[O:3])[CH3:30]
Reactant: O=C(O)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c(F)n1
Reactant: CCI
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c(F)n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 4-carboxy-2-fluoro-1-triphenylmethylimidazole (280 mg.) in THF (0.75 ml.) was treated, under argon with 1,5-diazabicyclo-5,4,0-undec-5-ene (0.112 ml.) followed by ethyl iodide (0.069 ml.). The mixture was stirred for two hours at room temperature, water was added and the mixture extracted, with ether. The ether extract was dried (MgSO4) and evaporated to give 4-ethoxycarbonyl-2-fluoro-1-triphenylmethylimidazole (185 mg.) as a yellow foam having the following n.m.r. in CDCl3 : 1.38 (t, 3H); 4.36 (q, 2H); 7.0-7.5 (m, 16H).
Reaction SMILES: [OH:1][CH:2]([CH:9]1[CH2:14][CH:13]2[CH2:15][CH:10]1[CH:11]=[CH:12]2)[CH2:3][CH2:4][CH2:5][CH2:6][O:7][CH3:8].[C:16](OC(=O)C)(=[O:18])[CH3:17].O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:16]([O:1][CH:2]([CH:9]1[CH2:14][CH:13]2[CH2:15][CH:10]1[CH:11]=[CH:12]2)[CH2:3][CH2:4][CH2:5][CH2:6][O:7][CH3:8])(=[O:18])[CH3:17]
Reactant: CC(=O)OC(C)=O
Reactant: COCCCCC(O)C1CC2C=CC1C2
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: O
Product: COCCCCC(OC(C)=O)C1CC2C=CC1C2
Yield: 97 %

Procedure:
In 63.3 g of pyridine, 105.2 g of 5-(1-hydroxy-5-methoxypentyl)-2-norbornene (Monomer 1) was reacted with 61.3 g of acetic anhydride in the presence of 2 g of 4-dimethylaminopyridine at room temperature for 10 hours. The reaction was stopped by adding 30 g of water. Extraction with hexane gave the organic layer, which was washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuum. The oily matter thus obtained was distilled in vacuum, obtaining 122.4 g of 5-(1-acetoxy-5-methoxypentyl)-2-norbornene. The yield was 97.0%.
Reaction SMILES: [F:1][C@@H:2]1[C@@H:6]([CH2:7][OH:8])[O:5][C@@H:4]([N:9]2[C:19]3[N:18]=[C:16]([NH2:17])[NH:15][C:13](=[O:14])[C:12]=3[N:11]=[CH:10]2)[CH2:3]1.[C:20]([NH:30][C@H:31]([C:35]([O:37][CH2:38][CH:39]([O:43][C:44](=[O:62])[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH3:61])[C:40](O)=[O:41])=[O:36])[CH:32]([CH3:34])[CH3:33])([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.CN(C=O)C>[F:1][C@@H:2]1[C@@H:6]([CH2:7][O:8][C:40](=[O:41])[CH:39]([O:43][C:44](=[O:62])[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH3:61])[CH2:38][O:37][C:35](=[O:36])[C@H:31]([CH:32]([CH3:33])[CH3:34])[NH:30][C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[O:5][C@@H:4]([N:9]2[C:19]3[N:18]=[C:16]([NH2:17])[NH:15][C:13](=[O:14])[C:12]=3[N:11]=[CH:10]2)[CH2:3]1
Reactant: CCCCCCCCCCCCCCCCCC(=O)OC(COC(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C)C(=O)O
Reactant: Nc1nc2c(ncn2[C@H]2C[C@H](F)[C@@H](CO)O2)c(=O)[nH]1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCCC(=O)OC(COC(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C)C(=O)OC[C@H]1O[C@@H](n2cnc3c(=O)[nH]c(N)nc32)C[C@@H]1F
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 2′,3′-dideoxy-3′-fluoroguanosine (404 mg, 1.5 mmole), 3-(N-CBZ-L-valyloxy)-2-stearoyloxy-propanoic acid (1.06 g, 1.75 mmole), DMAP (24 mg, 0.2 mmole) and HOBT (264 mg, 1.82 mmole) was coevaporated two times with DMF and reduced to about 30 ml. DCC (372 mg, 1.8 mmole) was added and the mixture was stirred overnight at room temperature. The mixture was filtered and the solution was evaporated under reduced pressure. Ethyl acetate (50 ml) was added and the organic phase was washed twice with 5% acetic acid, with 5% sodium hydrogen carbonate and with water. The organic phase was dried with sodium sulfate and evaporated under reduced pressure. The product was isolated by silica gel column chromatography. Yield: 0.73 g
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[C:12]([O:18][CH2:19][CH3:20])(=[O:17])[CH2:13][C:14]([CH3:16])=[O:15].N1CCCCC1.C(O)(=O)C>C1C=CC=CC=1>[C:14]([C:13](=[CH:7][C:6]1[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)[C:12]([O:18][CH2:19][CH3:20])=[O:17])(=[O:15])[CH3:16]
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: CCOC(=O)CC(C)=O
Solvent: C1CCNCC1
Solvent: CC(=O)O
Solvent: c1ccccc1
Product: CCOC(=O)C(=Cc1cccc([N+](=O)[O-])c1)C(C)=O
Temperature: 25 °C
Yield: 69.1 %

Procedure:
A reaction mixture containing m-nitrobenzaldehyde (151 g; 1.0 mole), ethyl acetoacetate (130 g; 1.0 mole), piperidine (4 mL) and glacial acetic acid (12 mL) in 200 mL benzene was refluxed for 2.5 hr while removing water (19 mL) by means of a Dean Stark trap. The dark brown reaction solution was allowed to cool to room temperature and was then water washed several times and concentrated in vacuo to give a dark yellow solid. This solid was recrystallized from ethanol to yield 182 g (69% yield) of yellow solid, m.p. 103°-106° C. Literature m.p.: S. Ruhemann, J. Chem. Soc., Vol 83, 717 (1903)--m.p. 110° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[NH:4][C:5]1[O:6][C:7]2[C:13](I)=[CH:12][CH:11]=[C:10]([O:15][CH3:16])[C:8]=2[N:9]=1.[Cl-].[Li+].[F:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.COCCOC>[CH3:1][O:2][C:3](=[O:17])[NH:4][C:5]1[O:6][C:7]2[C:13]([C:24]3[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=3)=[CH:12][CH:11]=[C:10]([O:15][CH3:16])[C:8]=2[N:9]=1
Reactant: COC(=O)Nc1nc2c(OC)ccc(I)c2o1
Reactant: OB(O)c1ccc(F)cc1
Agent: O=C([O-])O
Agent: [Cl-]
Agent: [Li+]
Solvent: C1COCCO1
Solvent: COCCOC
Product: COC(=O)Nc1nc2c(OC)ccc(-c3ccc(F)cc3)c2o1
Temperature: 100 °C
Yield: 97.9 %

Procedure:
To a stirred solution of 3.00 g (8.62 mmol) (7-iodo-4-methoxy-benzooxazol-2-yl)-carbamic acid methyl ester in 20 ml dioxane and 60 ml 1,2-dimethoxyethane were added 731 mg (17.2 mmol) lithium chloride, 299 mg (0.26 mmol) tetrakis(triphenyl-phosphine)palladium(0), 1.45 g (10.3 mmol) para-fluorobenzeneboronic acid and 18 ml of a 1 N aq. solution of sodium bicarbonate. The mixture was heated at 100° C. for 24 h and then poured onto water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Trituration in ether afforded 2.67 g (98%) [7-(4-fluoro-phenyl)-4-methoxy-benzooxazol-2-yl]-carbamic acid methyl ester as an off-white solid. ES-MS m/e (%): 317 (M+H+, 100).
Reaction SMILES: [C:1]([N:3]=[C:4]([C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)OC(C)C)#[N:2].[CH2:15]([NH2:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CO>[C:1]([NH:3][C:4]([C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)=[N:22][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)#[N:2]
Reactant: NCc1ccccc1
Reactant: CC(C)OC(=NC#N)c1cccnc1
Solvent: CO
Product: N#CNC(=NCc1ccccc1)c1cccnc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 69.2 %

Procedure:
Isopropyl N-cyano-3-pyridinecarboximidate (0.50 g, 2.6 mmol) was dissolved in methanol (10 ml), and benzylamine (0.31 g, 2.9 mmol) was added. The mixture was stirred at room temperature for 30 minutes. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the concentrated residue thus obtained was crystallized from methanoldiethyl ether to give the title compound (0.44 g, 1.8 mmol, yield: 72%) as colorless needles.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C1(C)C=CC=CC=1.C1COCC1.[C:19]1([C:25]2([C:29]#[N:30])[CH2:28][CH2:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[OH-].[Na+]>C1COCC1.O>[C:19]1([C:25]2([CH2:29][NH2:30])[CH2:28][CH2:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: N#CC1(c2ccccc2)CCC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: C1CCOC1
Product: NCC1(c2ccccc2)CCC1
Temperature: 0 °C
Yield: 74.4 %

Procedure:
A commercial suspension of LiAlH4 at 13% in a toluene-THF mixture, under nitrogen (0.595 mole; 175 ml), diluted with 270 ml of THF is maintained at 0° C. A mixture of 90 g (0.572 mole) of 1-phenylcyclobutanecarbonitrile and 800 ml of THF is added dropwise during 20 minutes. After the addition, the temperature is slowly allowed to rise before heating to reflux during 1 hour. After cooling at about 5° C., 150 ml water, 150 ml 10% NaOH and again 560 ml water are poured dropwise with care. The mixture is extracted with ethyl acetate after having saturated the aqueous phase with NaCl. The organic phase is extracted with a N HCl solution. This aqueous phase is made basic by means of 30% NaOH and is extracted with dichloromethane, which, after washing with water, drying over Na2SO4 and concentration gives a reddish liquid which is purified by distillation. There is obtained 68.65 g (yield=81.3%) of a colorless liquid. b.p.6 =84°-92° C.