Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+](C1C=CC(O[C:11](=[O:30])/[CH:12]=[CH:13]/[CH:14]=[C:15](/[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)\[C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=CC=1)([O-])=O.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][CH2:38][CH2:39][CH2:40][NH2:41])[CH:32]=1>O1CCCC1>[CH3:29][O:28][C:25]1[CH:24]=[CH:23][C:22](/[C:15](/[C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:14]/[CH:13]=[CH:12]/[C:11]([NH:41][CH2:40][CH2:39][CH2:38][CH2:37][C:33]2[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=2)=[O:30])=[CH:27][CH:26]=1
Reactant: NCCCCc1cccnc1
Reactant: COc1ccc(/C(=C/C=C/C(=O)Oc2ccc([N+](=O)[O-])cc2)c2cccnc2)cc1
Solvent: C1CCOC1
Product: COc1ccc(/C(=C/C=C/C(=O)NCCCCc2cccnc2)c2cccnc2)cc1
Yield: 79.9 %

Procedure:
As before in Example 134, a solution of (2E,4Z)-5-(4-methoxyphenyl)-5-(3-pyridinyl)-2,4-pentadienoic acid 4-nitrophenyl ester (2.01 g) and 3-pyridinebutanamine (0.75 g) in tetrahydrofuran (25 mL) was stirred for 17 hours at room temperature. After the usual workup. the crude product was crystallized from ethyl acetate to yield 1.65 g of (2E,4Z)-5-(4-methoxyphenyl)-5-(3-pyridinyl)-N-[4-(3-pyridinyl)butyl]-2,4-pentadienamide mp 108°-110° C. Recrystallization of a portion from the same solvent provided the analytical sample, mp 109°-110° C.
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:19]3=[N:20][CH:21]=[CH:22][CH:23]=[C:18]3[NH:17][N:16]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].FC(F)(F)S(O[CH2:36][CH:37]([F:39])[F:38])(=O)=O.O>CN(C=O)C>[F:38][CH:37]([F:39])[CH2:36][N:17]1[C:18]2[C:19](=[N:20][CH:21]=[CH:22][CH:23]=2)[C:15]([C:12]2[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=2)=[N:16]1
Reactant: c1ccc(COc2ccc(-c3n[nH]c4cccnc34)cc2)cc1
Reactant: O=S(=O)(OCC(F)F)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: Oc1ccc(-c2nn(CC(F)F)c3cccnc23)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 51.8 %

Procedure:
To a stirred mixture of 3-[4-(benzyloxy)phenyl]-1H-pyrazolo[4,3-b]pyridine (300 mg) and Cs2CO3 (649 mg) in DMF (4 ml) was added 2,2-difluoroethyl trifluoromethanesulfonate (234 mg) at 0° C. The mixture was stirred at room temperature for 12 h, treated with water, and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue was dissolved in EtOH (8 mL) and 10% Pd—C (200 mg) was added. The mixture was stirred at room temperature for 30 min under H2 atmosphere, filtered and evaporated. The residue was purified by silica gel column chromatography (hexane/AcOEt) to give the title compound (142 mg).
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH2:12][CH:13]([NH2:15])[CH3:14])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[F:16][CH:17]([F:28])[C:18]1[C:22]([C:23](O)=[O:24])=[C:21]([F:26])[N:20]([CH3:27])[N:19]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[Cl:1][C:2]1[C:3]([CH2:12][CH:13]([NH:15][C:23]([C:22]2[C:18]([CH:17]([F:28])[F:16])=[N:19][N:20]([CH3:27])[C:21]=2[F:26])=[O:24])[CH3:14])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1
Reactant: CC(N)Cc1ncc(C(F)(F)F)cc1Cl
Reactant: Cn1nc(C(F)F)c(C(=O)O)c1F
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(Cc1ncc(C(F)(F)F)cc1Cl)NC(=O)c1c(C(F)F)nn(C)c1F
Reaction time: 8 h
Yield: 82.7 %

Procedure:
At ambient temperature, 150 mg (0.545 mmol) of 1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-amine, 116 mg (0.60 mmol) of 3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxylic acid, 81 mg (0.60 mmol) of 1-hydroxybenzotriazole and 55 mg (0.545 mmol) of triethylamine are stirred together in 1 ml of dimethylformamide until dissolution. This solution is pourred over a 2 g-containing basic alumina Chem-Elut™ cartridge packed with 1.48 g of Si-DCC resin (1.09 mmol of DCC per g of resin) and left overnight at ambient temperature. The cartridge is then washed three times by 2 ml of acetonitrile. The solvents are removed and the crude amide is purified by column chromatography on silica gel (gradient heptane/ethyl acetate) to yield 187 mg (78% yield) of N-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propan-2-yl}-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide as yellow solid (M+H=415).
Reaction SMILES: [N:1]([C:4]1[CH2:5][C@@H:6]2[CH2:23][C:22](=[O:24])[N:7]2[C:8]=1[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=1)=[O:10])=[N+]=[N-].[C:25]([O:28][CH:29]=[CH2:30])(=[O:27])[CH3:26].C(=O)(O)[O-].[Na+]>ClCCl>[C:25]([O:28][CH:29]1[CH2:30][N:1]1[C:4]1[CH2:5][C@@H:6]2[CH2:23][C:22](=[O:24])[N:7]2[C:8]=1[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=1)=[O:10])(=[O:27])[CH3:26]
Reactant: C=COC(C)=O
Reactant: [N-]=[N+]=NC1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)C[C@H]2C1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(=O)OC1CN1C1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)C[C@H]2C1
Reaction time: 48 h
Yield: 41 %

Procedure:
A mixture of p-nitrobenzyl 2-azido-carbapen-2-em-3-carboxylate (11.3 mg, 34 micromol), vinyl acetate (0.1 ml), and solid sodium bicarbonate in dry dichloromethane was kept 2 days at ambient temperature, filtered through florisil, and evaporated under vacuum. The residue was chromatographed on one 15 cm×20 cm 250 micron silica gel preparative thin layer chromatography plate developed with 5:1 (v/v) diethyl ether-ethyl acetate. The band centered at Rf 0.20 was eluted with ethyl acetate and the eluate was evaporated under vacuum to provide 5.5 mg (41%) p-nitrobenzyl 2-(2-acetoxyaziridin-1-yl)-carbapen-2-em-3-carboxylate; IR (CH2Cl2): 1770, 1735 cm-1 ; NMR (CDCl3): δ 1.90 dd (J1 =6 Hz, J2 =7 Hz, 1H), 2.10 t (J=7 Hz, 1H), 2.13 s (3H), 2.76 bd (J=5 Hz, 2H), 2.85 dd (J 1 =2.5 Hz, J2 =15 Hz, 1H), 3.25 dd (J1 =5 Hz, J2 =15 Hz, 1H), 4.12 m (1H), 4.87 dd (J1 =6 Hz, J2 =7 Hz, 1H), 5.27 s (2H), 7.49 d (J=9 Hz, 2H), 8.25 d (J=9 Hz, 2H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:64])[C@H:4]1[O:51][C@@H:8]([O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[N:17]([CH2:34][C:35]4[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH2:43][N:44]5[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]5)=[CH:37][CH:36]=4)[C:18]4[C:23]([C:24]=3[CH3:25])=[CH:22][C:21]([O:26]CC3C=CC=CC=3)=[CH:20][CH:19]=4)=[CH:12][CH:11]=2)[C@:7]([C:53](=[O:55])[CH3:54])([OH:52])[C@@:6]([C:57](=[O:59])[CH3:58])([OH:56])[C@@H:5]1[O:60][C:61](=[O:63])[CH3:62]>C1COCC1.CO.[Pd]>[CH3:1][O:2][C:3](=[O:64])[C@H:4]1[O:51][C@@H:8]([O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[N:17]([CH2:34][C:35]4[CH:36]=[CH:37][C:38]([O:41][CH2:42][CH2:43][N:44]5[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50]5)=[CH:39][CH:40]=4)[C:18]4[C:23]([C:24]=3[CH3:25])=[CH:22][C:21]([OH:26])=[CH:20][CH:19]=4)=[CH:12][CH:11]=2)[C@:7]([C:53](=[O:55])[CH3:54])([OH:52])[C@@:6]([C:57](=[O:59])[CH3:58])([OH:56])[C@@H:5]1[O:60][C:61](=[O:63])[CH3:62]
Reactant: COC(=O)[C@H]1O[C@@H](Oc2ccc(-c3c(C)c4cc(OCc5ccccc5)ccc4n3Cc3ccc(OCCN4CCCCCC4)cc3)cc2)[C@@](O)(C(C)=O)[C@](O)(C(C)=O)[C@@H]1OC(C)=O
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: COC(=O)[C@H]1O[C@@H](Oc2ccc(-c3c(C)c4cc(O)ccc4n3Cc3ccc(OCCN4CCCCCC4)cc3)cc2)[C@@](O)(C(C)=O)[C@](O)(C(C)=O)[C@@H]1OC(C)=O

Procedure:
Glycosidated indole 34 (3.7 g, 4.2 mmol) in 60 mL THF/MeOH (1:1) was treated with 10% Pd/C (1.5 g) and hydrogenated in a Parr apparatus at 40 psi for 23 h. The reaction mixture was filtered through a bed of Celite and the filter cake was washed with THF (20 mL) and EtOH (20 mL). To avoid any air oxidation, L-ascorbic acid (0.37 g) was added to the filtered solution. The solution was concentrated and chromatographed on silica gel using CHCl3/i-PrOH (7:1) to render the product 35 (1.6 g, 48%) as a brown foam: Rf=0.20 (7:1 CHCl3:iPrOH); 1H NMR (DMSO) 6.5-7.5 (m, 11H), 5.7 (d, 1H, J=7.9 Hz), 5.5 (t, 1H, J=9.6 Hz), 4.9-5.2 (m, 4H), 4.7 (d, 1H, J=9.9 Hz), 3.6 (s, 3H), 3.3 (s, 8H), 2.1 (s, 3H), 1.9-2.2 (m, 9H), 1.5-1.9 (m, 8H); 13C NMR (CDCl3) 170.0, 169.0, 167.0, 157.0, 156.5, 150.0, 138.0, 131.7, 131.6, 130.0, 127.3, 116.9, 114.7, 112.0, 111.0, 108.0, 104.5, 98.8, 72.6, 71.8, 71.1, 69.1, 64.4, 55.0, 55.2, 53.0, 47.0, 26.7, 23.6, 20.6, 20.5, 9.5; IR (KBr): νmax 3427, 3037, 2935, 2612, 1757, 1612, 1510, 1462, 1374, 1227, 1040 cm−1; LC/MS (ESI) retention time=13.0, M+H+=787.
Reaction SMILES: [CH3:1][C@H:2]1[C:6](=[O:7])[O:5][C:4](=[O:8])[NH:3]1.[C:9](Cl)(=[O:19])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].CN1CCOCC1>C(OCC)(=O)C>[C:9]([N:3]1[C@@H:2]([CH3:1])[C:6](=[O:7])[O:5][C:4]1=[O:8])(=[O:19])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: C[C@@H]1NC(=O)OC1=O
Reactant: CCCCCCCCCC(=O)Cl
Solvent: CN1CCOCC1
Solvent: CCOC(C)=O
Product: CCCCCCCCCC(=O)N1C(=O)OC(=O)[C@@H]1C
Reaction time: 2 h
Yield: 65 %

Procedure:
(S)-4-methyl-2, 5-oxazolidinedione (L-alanine-NCA) (345 mg, 3 mmol) was dissolved in ethyl acetate (20 mL), followed by the addition of decanoyl chloride (744 mg, 3.9 mmol) under ice cooling. Further, a solution of N-methylmorpholine (394 mg, 3.9 mmol) in ethyl acetate (10 mL) was added dropwise under ice cooling over 20 minutes, and the resulting mixture was then stirred at the same temperature for 2 hours, the reaction mixture was treated in a similar manner as in Synthesis Process 5 of Example 8 to afford the title compound (525 mg, 65%) as a colorless clear syrup. A portion of the thus-obtained syrup was recrystallized from hexane to obtain white crystals (280 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:13]#[N:14])=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-])=O>CCO.[Pd]>[NH2:1][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:13]#[N:14])=[CH:9][NH:10]2)=[CH:6][CH:5]=1
Reactant: N#Cc1c[nH]c2cc([N+](=O)[O-])ccc12
Agent: [Pd]
Solvent: CCO
Product: N#Cc1c[nH]c2cc(N)ccc12
Yield: 25.4 %

Procedure:
A suspention of 6-nitro-1H-indole-3-carbonitrile (4.6 g, 25 mmol) and 10% Pd—C (0.46 g) in EtOH (50 mL) was stirred under H2 (1 atm) at room temperature overnight. After filtration, the filtrate was concentrated and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate=3/1) to give 6-amino-1H-indole-3-carbonitrile (1.0 g, 98%) as a pink solid. 1H NMR (DMSO-d6) δ 11.51 (s, 1H), 7.84 (d, J=2.4 Hz, 1H), 7.22 (d, J=8.4 Hz, 1H), 6.62 (s, 1H), 6.56 (d, J=8.4 Hz, 1H), 5.0 (s, 2H); MS (ESI) m/e (M+H+) 157.1.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4]([S:20][NH2:21])[N:3]=1.O.CC(C)=[O:25].ClC1C=C(C=CC=1)C(OO)=O>C(O)C>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4]([S:20]([NH2:21])=[O:25])[N:3]=1
Reactant: CC(C)=O
Reactant: NSc1nc(N)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: O
Solvent: CCO
Product: Nc1nc(S(N)=O)c2ncn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2n1
Temperature: 0 °C

Procedure:
A mixture of 2-amino-9-β-D-ribofuranosyl-9H-purine-6-sulfenamide (18) (1.57 g, 0.005 mol), ethanol (700 mL) and water (50 mL) was vigorously stirred and cooled in an ice bath. After the temperature of the suspension had decreased to <10° C., acetone was added to the ice bath to obtain a temperature of <0° C. With continual stirring a solution of commercially available (Aldrich Chem Co.) 3-chloroperoxybenzoic acid (80-85%, 1.0 g, 0.0046-0.0049 mol) in ethanol (40 mL) was added dropwise over a period of approx. 15 min. The reaction flask was stoppered, the mixture was allowed to stir and warm as the ice melted, and then stirred at ambient temperature for a total reaction time of 19 hr. The reaction mixture was filtered (Whatman GF/A glass microfiber filter) to remove a trace of undissolved solid and then the filtrate was evaporated in vacuo and at a temperature of >25° C. to near dryness. The product was washed from the evaporation flask with acetone (50-100 mL) and the solid was collected by filtration, suspended in diethyl ether (50 mL), refiltered, dried under vacuum at ambient temperature: (1.3 g, 0.0042 mol, 85%), m.p. 183°-185° C. dec. with prior sintering and darkening. IR (KBr): 1040 (vs, S=O), 3000-3600 (NH2, OH)cm-1 : UV: λmax (pH 1) 333 nm (ε2,900): λmax (pH 7) 326 nm (ε10,700): λmax (pH 11) 325 nm (ε8,700): 1H NMR (DMSO-d6): δ 5.85 (d, 1, J =5.52 Hz, C1'H), 6.49 (s, 2, SONH2, exchanged with D2O), 6.98 (s, 2, NH2, exchanged with D2O), 8.45 (s, 1, C8 e,uns/H/ ), and other sugar protons. Anal. Calcd. for C10H14N6O5S.1/2C2H5OH (353.32): C, 37.39: H, 4.82: N, 23.80: S, 9.07. Found: C, 37.29: H, 4.56: N, 23.78: S, 8.92.
Reaction SMILES: [CH2:1]([CH:3]1[O:5][CH2:4]1)Cl.C([O-])([O-])=O.[K+].[K+].[C:12]([C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)#[N:13]>C(#N)C>[O:5]1[CH2:4][CH:3]1[CH2:1][O:20][C:17]1[CH:18]=[CH:19][C:14]([C:12]#[N:13])=[CH:15][CH:16]=1
Reactant: ClCC1CO1
Reactant: N#Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: N#Cc1ccc(OCC2CO2)cc1
Yield: 75 %

Procedure:
Epichlorohydrin (800 mL) and K2CO3 (414 g) were added to a stirred solution of p-cyanophenol (238 g) in 2.0 L of acetonitrile. The reaction mixture was brought to reflux under an inert atmosphere for 2 h before being filtered whilst still hot. The resulting filtrate was concentrated to give a clear oil. This was crystallized from di-iso-propyl ether to give the sub-title compound in a 75% yield.
Reaction SMILES: C([N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]([CH3:14])[CH2:5]1)(=O)C.C(O[CH:18]=[C:19]([C:25]([O:27]CC)=O)[C:20]([O:22]CC)=[O:21])C.O.[OH-].[Na+]>C(O)(=O)C>[CH3:14][CH:6]1[N:7]2[CH:18]=[C:19]([C:20]([OH:22])=[O:21])[C:25](=[O:27])[C:9]3[C:8]2=[C:13]([CH:12]=[CH:11][CH:10]=3)[NH:4][CH2:5]1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: CC(=O)N1CC(C)Nc2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Product: CC1CNc2cccc3c(=O)c(C(=O)O)cn1c23
Temperature: 120 °C

Procedure:
A mixture of 0.0894 mole (1.7 g) of optically purified (+) 1-acetyl-3-methyl-1,2,3,4-tetrahydroquinoxaline and 0.009 mole (1.9 g) diethyl ethoxymethylenemalonate was heated over one hour to 200° C. and maintained at that temperature for 1.5 hours. After cooling, 5 g of polyphosphoric acid were added and the mixture was heated at 120° C. until foaming stops. The mixture was stirred into water and the solution was made strongly basic with 25 percent sodium hydroxide. The solution was stirred and heated on a steam bath for one hour, then neutralized with acetic acid. Cooling, followed by filtration provided an olive green solid R(+) 2,3-dihydro-3-methyl-7-oxopyrido-[1,2,3-de]quinoxaline-6- carboxylic acid, m.p. >250° C. Analysis: Calculated for C13H12N2O3 : %C, 63.9; %H, 5.0; %N, 11.5; Found: %C, 63.4; %H, 5.0; %N, 11.6. Optical rotation [α]21 D = 93±3° (C=0.594, N,N-dimethylformamide:ethanol, 1/1).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[Cl-].[NH4+].[CH3:7][C:8]([CH3:13])([CH3:12])[CH:9]1[O:11][CH2:10]1>CO.O>[N:1]([CH2:10][CH:9]([OH:11])[C:8]([CH3:13])([CH3:12])[CH3:7])=[N+:2]=[N-:3]
Reactant: CC(C)(C)C1CO1
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CC(C)(C)C(O)CN=[N+]=[N-]
Temperature: 0 °C
Yield: 93.8 %

Procedure:
Sodium azide (10 g, 154 mmol) and ammonium chloride (3.7 g, 070 mmol) are added to a solution of 3,3-dimethyl-1,2-epoxybutane (4.26 ml, 35 mmol) in methanol:water (8:1, 315 ml), and the mixture is heated at reflux for 7 hours. The reaction is poured into ice/water (400 ml) and extracted with dichloromethane (3×200 ml). The combined organics are dried (MgSO4), filtered and evaporated to yield a clear oil (4.7 g, 94 %).
Reaction SMILES: [CH3:1][C:2]([C:5]1[C:6]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[S:22]([CH3:25])(=[O:24])=[O:23])=[N:7][C:8]2[C:13]([CH:14]=1)=[N:12][CH:11]=[C:10]([F:15])[CH:9]=2)(O)C.[C:26]1(=[O:36])[NH:30][C:29](=[O:31])[C:28]2=[CH:32][CH:33]=[CH:34][CH:35]=[C:27]12.N(C(OC(C)C)=O)=NC(OC(C)C)=O.O>C1COCC1>[F:15][C:10]1[CH:9]=[C:8]2[C:13]([CH:14]=[C:5]([CH:2]([N:30]3[C:26](=[O:36])[C:27]4[C:28](=[CH:32][CH:33]=[CH:34][CH:35]=4)[C:29]3=[O:31])[CH3:1])[C:6]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[S:22]([CH3:25])(=[O:23])=[O:24])=[N:7]2)=[N:12][CH:11]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CC(C)(O)c1cc2ncc(F)cc2nc1-c1ccccc1S(C)(=O)=O
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Solvent: O
Solvent: C1CCOC1
Product: CC(c1cc2ncc(F)cc2nc1-c1ccccc1S(C)(=O)=O)N1C(=O)c2ccccc2C1=O
Reaction time: 0.17 h

Procedure:
To a mixture of methyl 1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)-1,5-naphthyridin-3-yl)ethanol (500 mg, 1.44 mmol) and phthalimide (425 mg, 2.88 mmol) in THF (15 mL) was added triphenylphosphene (757 mg, 2.88 mmol) at 0° C. The reaction mixture was stirred for 10 min at same temperature. Diisopropyl azo-dicarboxylate (0.6 mL, 2.88 mmol) was added to reaction mixture at 0° C. The reaction mixture was stirred for overnight at 0° C. Water was added to reaction mixture and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo to give 2-(1-(7-fluoro-2-(2-(methylsulfonyl)phenyl)-1, 5-naphthyridin-3-yl)ethyl) isoindoline-1,3-dione: LC-MS (ESI) m/z 476.0 [M+H]+. It was carried on crude for next step.
Reaction SMILES: ON1C2C=CC=CC=2N=N1.[CH3:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([C:35](O)=[O:36])=[C:20]([CH2:22][N:23]3[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[N:25]=[C:24]3[CH2:32][CH2:33][CH3:34])[S:21][C:15]=2[N:14]([CH2:38][CH:39]([CH3:41])[CH3:40])[C:13]1=[O:42].Cl.C(N=C=NCCCN(C)C)C.Cl.[CH3:56][NH:57][O:58][CH3:59]>ClCCl.C(N(CC)CC)C>[CH3:59][O:58][N:57]([CH3:56])[C:35]([C:19]1[C:16]2[C:17](=[O:18])[N:12]([CH3:11])[C:13](=[O:42])[N:14]([CH2:38][CH:39]([CH3:40])[CH3:41])[C:15]=2[S:21][C:20]=1[CH2:22][N:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=[C:24]1[CH2:32][CH2:33][CH3:34])=[O:36]
Reactant: CCCc1nc2ccccc2n1Cc1sc2c(c1C(=O)O)c(=O)n(C)c(=O)n2CC(C)C
Reactant: CNOC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCc1nc2ccccc2n1Cc1sc2c(c1C(=O)N(C)OC)c(=O)n(C)c(=O)n2CC(C)C
Reaction time: 0.08 h

Procedure:
1-Hydroxybenzotriazole (0.14 g) was added to a solution of the product of step b) (0.25 g) in dichloromethane (5 ml). After stirring for 5 minutes, 1-ethyl-3-(3′-dimethylaminopropyl)-carbodiimide hydrochloride (0.21 g) was added. After stirring for 10 minutes, N,O-dimethylhydroxylamine hydrochloride (0.1 g) and triethylamine (0.15 ml) were added The reaction mixture was stirred for 12 h at room temperature. The solution was concentrated in vacuo. The residue was purified by flash silica chromatography eluting with a gradient of 0-3% methanol in dichloromethane to give the title compound as a yellow solid (0.118 g).
Reaction SMILES: C(OC([NH:8][C:9]([NH:18][CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]1[N:29]2[N:30]=[C:31]([C:45]3[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=3)[C:32]([C:33]3[CH:38]=[CH:37][N:36]=[C:35]([NH:39][CH:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)[N:34]=3)=[C:28]2[CH:27]=[CH:26][CH:25]=1)=[N:10]C(OC(C)(C)C)=O)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH:40]1([NH:39][C:35]2[N:34]=[C:33]([C:32]3[C:31]([C:45]4[CH:46]=[CH:47][C:48]([O:51][CH3:52])=[CH:49][CH:50]=4)=[N:30][N:29]4[C:24]([NH:23][CH2:22][CH2:21][CH2:20][CH2:19][NH:18][C:9]([NH2:10])=[NH:8])=[CH:25][CH:26]=[CH:27][C:28]=34)[CH:38]=[CH:37][N:36]=2)[CH2:44][CH2:43][CH2:42][CH2:41]1
Reactant: COc1ccc(-c2nn3c(NCCCCNC(=NC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)cccc3c2-c2ccnc(NC3CCCC3)n2)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(-c2nn3c(NCCCCNC(=N)N)cccc3c2-c2ccnc(NC3CCCC3)n2)cc1
Yield: 32.4 %

Procedure:
To a solution of N,N″-di-tert-butoxycarbonyl-N′-(4-{[3-[2-(cyclopentylamino)-pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]amino}butyl)-guanidine (42 mg, 0.06 mmol) in dichloromethane (8 mL) was added trifluoroacetic acid (2 mL). The resultant solution was stirred for 8 hours and then concentrated in vacuo. The residue was dissolved in dichloromethane and saturated aqueous sodium bicarbonate was added. The organic layer was washed with brine. The aqueous layer was extracted with dichloromethane and the combined organics were dried over sodium sulfate. Filtration and concentration provided N-(4-{[3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-yl]amino}butyl)guanidine (10 mg, 33%) as a yellow solid. MS m/z 514 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:12]=2)=[CH:4][CH:3]=1.[OH:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34](O)=[O:35])=[CH:28][CH:27]=1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:12]=2)[C:34](=[O:35])[CH2:33][CH2:32][C:29]2[CH:30]=[CH:31][C:26]([OH:25])=[CH:27][CH:28]=2)=[CH:4][CH:3]=1
Reactant: O=C(O)CCc1ccc(O)cc1
Reactant: Fc1ccc(NCCc2cccc(OCc3ccccc3)c2)cc1
Product: O=C(CCc1ccc(O)cc1)N(CCc1cccc(OCc2ccccc2)c1)c1ccc(F)cc1
Yield: 88.9 %

Procedure:
The title compound was prepared as described in Example 44.D using (4-fluorophenyl){2-[3-(phenylmethoxy)phenyl]ethyl}amine (1.4 g, 4.36 mmol) and 3-(4-hydroxyphenyl)propanoic acid (1.01 g, 6.11 mmol) to provide the title compound (1.82 g, 89% yield): ES-MS (m/z) 470 [M+H]+.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].C([O-])([O-])=O.[K+].[K+].[CH2:18]([SH:21])[CH2:19][CH3:20]>CN(C=O)C>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([S:21][CH2:18][CH2:19][CH3:20])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1
Reactant: Cc1ccc(Cl)c([N+](=O)[O-])c1
Reactant: CCCS
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCSc1ccc(C)cc1[N+](=O)[O-]
Temperature: 70 °C
Yield: 91.4 %

Procedure:
A solution of 4-chloro-3-nitro-toluene (25 g, 145 mmol) in anhydrous DMF (200 ml) was treated with K2CO3 (40.29 g, 291 mmol) and 1-propane thiol (12.2 g, 160 mmol). The reaction mixture was heated to 70° C. for 12 h. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, diluted water and extracted with ethyl acetate (200 ml). The organic layer was washed with brine, dried over sodium sulphate and evaporated under reduced pressure, to give a crude which was purified by column chromatography (silica) using petroleum ether/ethyl acetate as eluent to afford the title compound (28 g, 91%) as a pale yellow solid.
Reaction SMILES: [CH:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:5][CH:4]=1)=[CH2:2].B1C2CCCC1CCC2.[OH-:30].[Na+].OO>C1COCC1.O>[OH:30][CH2:2][CH2:1][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:5][CH:4]=1
Reactant: C=Cc1ccc(NC(=O)OC(C)(C)C)c2ccccc12
Reactant: [OH-]
Agent: B1C2CCCC1CCC2
Agent: OO
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)Nc1ccc(CCO)c2ccccc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 86.2 %

Procedure:
To a solution of tert-butyl 4-vinylnaphthalen-1-ylcarbamate (31) (0.83 g, 3.08 mmol) in THF (10 mL) was added 9-BBN (0.5M in THF, 9.9 mL, 4.95 mmol) dropwise under nitrogen at 0° C. The mixture was warmed to RT and stirred for 16 hr. Water (1 mL), aqueous NaOH solution (3M, 10.0 mL, 30 mmol) and hydrogen peroxide (35% in water, 8.0 mL) were added. The reaction mixture was warmed to 50° C. and stirred for 2 hr and was then extracted with ethyl acetate. The ethyl acetate extract was washed with water and brine, dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 10-60% ethyl acetate in isohexane, gradient elution) to afford the title compound (32) (0.763 g, 86%); m/z 288 (M+H)+, (ES+).