Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN(C)P(N(C)C)(N(C)C)=O.[CH2:12]([N:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21][C:20]1=[O:29])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl[CH2:31][CH2:32][CH2:33][CH2:34]I.O>O1CCCC1>[CH2:12]([N:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][C:21]2([CH2:34][CH2:33][CH2:32][CH2:31]2)[C:20]1=[O:29])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: O=C1CCc2ccccc2N1Cc1ccccc1
Reactant: ClCCCCI
Solvent: C1CCOC1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: O
Product: O=C1N(Cc2ccccc2)c2ccccc2CC12CCCC2
Temperature: -22 °C
Reaction time: 16 h

Procedure:
To diethylamine (0.96 ml, 0.0092 mol) in 4 ml tetrahydrofuran at 0° C. was added butyllithium (5.8 ml of 1.6 M in hexane, 0.0092 mol) and the mixture stirred for 10 minutes at 0° C., then warmed to room temperature, thus forming a solution of lithium diethylimide. The solution was cooled to -22° C., hexamethylphosphoramide (4 ml) and then, over a 5 minutes period, 1-benzyl-3,4-dihydro-2(1H)-quinolone (1.0 g, 0.0042 mol) in 6 ml tetrahydrofuran were added, and the resulting mixture warmed to 15° C. over 1 hour, then recooled to -55° C., at which point a solution of 1-chloro-4-iodobutane (0.95 g, 1.03 molar equivalents) in 10 ml tetrahydrofuran was added over 5 minutes. After stirring 16 hours at -55° C., water (5 ml) was added and the mixture warmed to room temperature, poured into 30 ml H2O and extracted 3×15 ml ether. The organic layers wre combined, washed 4×20 ml H2O, dried (MgSO4) and stripped to dryness (1.32 g) and radially chromatographed on a thick layer plate of silica gel with CHCl3 as eluant to produce present title product, 0.48 g; mass spectra includes molecular ion at 291.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2[NH:17][C@H:18]1[CH2:23][CH2:22][C@H:21]([CH2:24][N:25]([CH3:27])[CH3:26])[CH2:20][CH2:19]1.[Cl:28][C:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[C:31]([F:44])[C:30]=1[OH:45].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>>[ClH:1].[ClH:28].[Cl:28][C:29]1[CH:34]=[C:33]([C:2]2[N:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12]([CH:14]2[CH2:16][CH2:15]2)=[O:13])=[C:5]3[NH:17][C@H:18]2[CH2:23][CH2:22][C@H:21]([CH2:24][N:25]([CH3:27])[CH3:26])[CH2:20][CH2:19]2)[CH:32]=[C:31]([F:44])[C:30]=1[OH:45]
Reactant: CC1(C)OB(c2cc(F)c(O)c(Cl)c2)OC1(C)C
Reactant: CN(C)C[C@H]1CC[C@H](Nc2c(C(=O)C3CC3)cnc3ccc(Cl)nc23)CC1
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Product: CN(C)C[C@H]1CC[C@H](Nc2c(C(=O)C3CC3)cnc3ccc(-c4cc(F)c(O)c(Cl)c4)nc23)CC1

Procedure:
Following general procedure II, (6-chloro-4-{trans-4-[(dimethylamino)methyl]-cyclohexyl amino}-1,5-naphthyridin-3-yl)(cyclopropyl)methanone (60 mg, 0.16 mmol) was reacted with 2-chloro-6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (61 mg, 0.23 mmol) followed by formation of the dihydrochloride salt to afford the desired product (54 mg, 61%) as a light yellow solid: 1H NMR (500 MHz, CD3OD) δ 9.41 (s, 1H), 8.45 (d, J=8.9 Hz, 1H), 8.34 (d, J=8.9 Hz, 1H), 8.02 (t, J=1.9 Hz, 1H), 7.88 (dd, J=11.6, 2.2 Hz, 1H), 5.73-5.64 (m, 1H), 3.09 (d, J=6.6 Hz, 2H), 2.94 (s, 6H), 2.93-2.83 (m, 1H), 2.48-2.40 (m, 2H), 2.10-1.96 (m, 3H), 1.73-1.61 (m, 2H), 1.46-1.34 (m, 2H), 1.34-1.18 (m, 4H). ESI MS m/z 497 [M+H]+; HPLC>99% (AUC), tR=10.26 min.
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:21][C:15]=3[O:14]2)(=O)=O)=CC=1.[N-:28]=[N+:29]=[N-:30].[Na+]>>[C:22]1([C:20]2[CH:19]=[CH:18][C:16]3[CH2:17][CH:13]([CH2:12][N:28]=[N+:29]=[N-:30])[O:14][C:15]=3[CH:21]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: [N-]=[N+]=[N-]
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3ccc(-c4ccccc4)cc3O2)cc1
Agent: [Na+]
Product: [N-]=[N+]=NCC1Cc2ccc(-c3ccccc3)cc2O1

Procedure:
Treatment of (±)-(6-phenyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.280 g, 0.736 mmol) with sodium azide (0.191 g, 2.94 mmol) generally according to the procedure described for Intermediate 98 gave (±)-(6-phenyl-2,3-dihydro-1-benzofuran-2-yl)methyl azide. Treatment of the azide with palladium on carbon (0.026 g, 10 wt. %) generally according to the procedure described for Example 1 provided 0.190 g (90%) of (±)-(6-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine as a tan solid, hydrobromide salt. mp 218-221° C. Anal. calcd. for C15H15NOHBr: C, 58.84; H, 5.27; N, 4.57. Found: C, 54.80; H, 4.88; N, 4.18.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH2:11]Br.[NH:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]1.[F-].[K+]>C(#N)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH2:11][N:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]1
Reactant: COc1cccc(OC)c1CBr
Reactant: CCOC(=O)C1CCNCC1
Agent: [F-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)C1CCN(Cc2c(OC)cccc2OC)CC1
Yield: 16.3 %

Procedure:
A stirred solution of 4.7 grams (0.020 mole) of 2,6-dimethoxyphenylmethyl bromide, 3.2 grams (0.020 mole) of ethyl piperidin-4-ylcarboxylate, and 23.5 grams (0.200 mole) of 50% potassium fluoride on Celite® filter aid in 100 mL of acetonitrile was heated at reflux for about 18 hours, after which the reaction mixture was cooled and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with mixtures of ethyl acetate in hexane as eluants. The product-containing fractions were combined and concentrated under reduced pressure to a residue. The residue was analyzed using thin layer chromatography, which indicated that the residue was impure. The residue was again subjected to column chromatography on silica gel, with mixtures of ethyl acetate in hexane and methanol in ethyl acetate as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about one gram of ethyl N-(2,6-dimethoxyphenylmethyl)piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [CH:1](=O)/[CH:2]=[CH:3]/[CH3:4].[C:6]1([S:12]([C:15]#[N:16])(=[O:14])=[O:13])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.Cl([O-])(=O)(=O)=O.[Li+]>>[C:6]1([S:12]([C:15]2[CH:4]=[CH:3][CH:2]=[CH:1][N:16]=2)(=[O:13])=[O:14])[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: C/C=C/C=O
Reactant: N#CS(=O)(=O)c1ccccc1
Agent: [Li+]
Agent: [O-][Cl+3]([O-])([O-])[O-]
Product: O=S(=O)(c1ccccc1)c1ccccn1
Temperature: 110 °C
Yield: 89.7 %

Procedure:
First, 8.05 g (113 mmol) of crotonaldehyde (2-butenal) and 9.17 g (54.9 mmol) of benzenesulfonyl cyanide were introduced to a 3-necked flask (50 ml volume) equipped with a thermometer, a magnetic stirrer, a Dean-Stark water type distilling receiver, and a condenser tube. Toluene (15 ml) as a solvent and butanol (1.5 ml) were added, and then 589 mg (5.55 mmol) of lithium perchlorate was added. Next, the mixture was heated under reflux for 15 hours while agitating at an internal temperature of 110° C. in a nitrogen atmosphere, and separating and removing water that was produced. After this solution was cooled to room temperature, the low-boiling components, such as solvent, etc., were removed under reduced pressure and the resulting concentrate was cooled in an ice bath to precipitate crystals. The crystals were filtered with a glass filter and washed with 10 ml of toluene that had been cooled to 5° C. or lower. Then the crystal were dried for 2 hours in vacuo to give 10.8 g of 2-benzenesulfonylpyridine having the following properties as colorless crystals (purity of 99%, yield of 89% based on benzenesulfonyl cyanide).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:23][CH2:24][C@@H:25]5[CH2:27][O:26]5)=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]=[CH:13][N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH:28]([NH:31][CH:32]([CH3:34])[CH3:33])([CH3:30])[CH3:29]>CN(C=O)C>[OH:26][C@@H:25]([CH2:27][N:31]([CH:32]([CH3:34])[CH3:33])[CH:28]([CH3:30])[CH3:29])[CH2:24][O:23][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([O:10][C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[NH:1][CH:2]=[CH:3]4)=[N:12][CH:13]=[N:14]2)=[CH:19][C:18]=1[O:21][CH3:22]
Reactant: COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1
Reactant: CC(C)NC(C)C
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN(C(C)C)C(C)C
Temperature: 70 °C
Reaction time: 19 h
Yield: 33.1 %

Procedure:
A mixture of (2S)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described for the starting material in Example 297), and diisopropylamine (0.45 ml, 3.2 mmol) in DMF (5 ml) was stirred at 70° C. for 19 hours under an atmosphere of nitrogen and then allowed to cool to ambient temperature. The solvents were removed in vacuo and the residue purified on silica gel, using gradient elution with dichloromethane/methanol (100/0 to 95/5), dichloromethane/methanolic ammonia (7M) (98/2 to 90/10) to give (2S)-7-(2-hydroxy-3-((N,N-diisopropyl)amino)propoxy)-4-(indol-5-yloxy)-6-methoxyquinazoline (43 mg, 33%).
Reaction SMILES: [C:1]([C:3]1[N:4]([CH3:24])[C:5]([C:14]2[S:15][C:16]3[N:17]=[CH:18][N:19]=[C:20]([NH2:23])[C:21]=3[N:22]=2)=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1)#[CH:2]>[Pd].CCOC(C)=O>[CH2:1]([C:3]1[N:4]([CH3:24])[C:5]([C:14]2[S:15][C:16]3[N:17]=[CH:18][N:19]=[C:20]([NH2:23])[C:21]=3[N:22]=2)=[C:6]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:7]=1)[CH3:2]
Reactant: C#Cc1nc(-c2ccccc2)c(-c2nc3c(N)ncnc3s2)n1C
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCc1nc(-c2ccccc2)c(-c2nc3c(N)ncnc3s2)n1C
Reaction time: 11 h
Yield: 32.9 %

Procedure:
10% Palladium on carbon (6 mg) was added to a solution of 2-(2-ethynyl-1-methyl-4-phenyl-1H-imidazol-5-yl)[1,3]thiazolo[5,4-d]pyrimidin-7-amine (Intermediate 46) (6 mg) in EtOAc (20 mL) under an inert atmosphere. The reaction mixture was then stirred under a hydrogen atmosphere for 11 hours, filtered and concentrated in vacuo. The impure product was triturated with diethyl ether and filtered to give the title compound as a colourless solid (2 mg, 30%);
Reaction SMILES: C([O:3][C:4]([C:6]1[N:11]2[N:12]=[C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])[N:14]=[C:10]2[CH:9]=[C:8]([C:21]2[CH:22]=[N:23][CH:24]=[N:25][CH:26]=2)[CH:7]=1)=O)C.[CH2:27]([NH2:29])[CH3:28]>CC(N(C)C)=O>[CH2:27]([NH:29][C:4]([C:6]1[N:11]2[N:12]=[C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])[N:14]=[C:10]2[CH:9]=[C:8]([C:21]2[CH:22]=[N:23][CH:24]=[N:25][CH:26]=2)[CH:7]=1)=[O:3])[CH3:28]
Reactant: CCNC(=O)Nc1nc2cc(-c3cncnc3)cc(C(=O)OCC)n2n1
Reactant: CCN
Solvent: CC(=O)N(C)C
Product: CCNC(=O)Nc1nc2cc(-c3cncnc3)cc(C(=O)NCC)n2n1
Temperature: 60 °C

Procedure:
A slurry of the product of Step 1 (0.268 g, 0.754 mmol) in dimethylacetamide (10 mL) was treated with ethylamine (2 mL, 30.6 mmol) then heated to 60° C. in a sealed tube for 16 h. The precipitate was filtered, washed with dimethylacetamide and then water, to give title compound as a solid; m.p. 317-321° C. ACPI-MS Found: [M+H]+=355.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:20])=[N:4][CH:5]=[C:6]([CH2:18][OH:19])[C:7]=1[CH2:8][NH:9][C:10]1[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=1.Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:29]([C:26]1[CH:27]=[CH:28][C:23]([CH2:22][O:1][C:2]2[C:3]([CH3:20])=[N:4][CH:5]=[C:6]([CH2:18][OH:19])[C:7]=2[CH2:8][NH:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)=[CH:24][CH:25]=1)#[N:30]
Reactant: Cc1ncc(CO)c(CNc2ccc(C#N)cc2)c1O
Reactant: N#Cc1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1ncc(CO)c(CNc2ccc(C#N)cc2)c1OCc1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 60 %

Procedure:
A mixture of 4-[(3-hydroxy-5-hydroxymethyl-2-methyl-pyridin-4-ylmethyl)-amino]-benzonitrile (1)* (404 mg, 1.5 mmol), α-bromo-p-tolunitrile (322 mg, 1.65 mmol), potassium carbonate (622 mg, 4.5 mmol) and DMF (10 mL) was stirred at room temperature under nitrogen atmosphere overnight. The reaction mixture was evaporated to dryness, and the crude product purified by column chromatography on silica gel using a gradient of dichloromethane:methyl alcohol (9:1) as eluant to give 4-{[3-(3-cyano-benzyloxy)-5-hydroxymethyl-2-methyl-pyridin-4-ylmethyl]-amino}-benzonitrile (2) (348 mg, 60% yield) as a colorless solid.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:3]([NH:5][C@@H:6]([CH2:14][CH2:15][C:16]([O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])=[O:17])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[O:4].C(N(C(C)C)CC)(C)C.[Br:43][CH2:44][C:45](Br)=[O:46].CO>O1CCCC1>[C:30]([O:29][C:27]([CH2:26][CH2:25][C@H:2]([NH:1][C:45](=[O:46])[CH2:44][Br:43])[C:3]([NH:5][C@@H:6]([CH2:14][CH2:15][C:16]([O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:22])[CH3:24])=[O:17])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[O:4])=[O:28])([CH3:33])([CH3:32])[CH3:31]
Reactant: CC(C)(C)OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(=O)OCC[Si](C)(C)C)C(=O)OC(C)(C)C
Reactant: O=C(Br)CBr
Solvent: CCN(C(C)C)C(C)C
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)CC[C@H](NC(=O)CBr)C(=O)N[C@@H](CCC(=O)OCC[Si](C)(C)C)C(=O)OC(C)(C)C
Reaction time: 1.5 h
Yield: 78.3 %

Procedure:
The product of step 7H (397 mg, 0.813 mmol) was dissolved in dry tetrahydrofuran (5 mL) with diisopropylethylamine (180 μL, 1.05 mmol) and cooled to —10° C. under nitrogen. Bromoacetyl bromide (85 μL, 0.98 mmol), dissolved in 10 mL tetrahydrofuran, was added dropwise to the cold solution, keeping T≦−5° C. The reaction was stirred in the cold for 1.5 hr, and 25 μL methanol added. The solids were filtered and rinsed and the combined filtrate concentrated to a brown oil, which was purified by flash chromatography (dichloromethane/ethyl acetate) to afford the product (388 mg, 78%) as a light tan oil. LRMS (ES): 609.3/611.3 [M+H]+, 631.3/633.3 [M+Na]+, 185.3, 144.2. 1HNMR (600.1343 MHz, CDCl3): 7.32 (m, 1H), 7.09 (m, 1H), 4.50 (m, 2H), 4.21 (m, 2H), 3.87 (m, 2H), 2.31 (m, 2H), 2.13 (m, 2H), 1.99 (m, 2H), 1.97 (m, 2H), 1.45 (s, 9H), 1.43 (s, 9H), 1.01 (m, 2H), 0.04 (s, 9H).
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.C1C(=O)N(Br)C(=O)C1.CSC.[N+](C1C=CC(C=NNC2C=CC(OC(F)(F)F)=CC=2)=CC=1)([O-])=O.[Br-].N1C=NN=N1.C(N(CC)CC)C>C(Cl)Cl.CCO>[F:25][C:2]([F:1])([F:24])[O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)=[N:11]2)=[CH:8][CH:9]=1
Reactant: O=[N+]([O-])c1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1
Agent: O=C1CCC(=O)N1Br
Agent: O=[N+]([O-])c1ccc(C=NNc2ccc(OC(F)(F)F)cc2)cc1
Agent: [Br-]
Solvent: CCN(CC)CC
Solvent: CCO
Solvent: ClCCl
Product: Nc1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1
Temperature: -20 °C
Reaction time: 2 h

Procedure:
1-(4-Trifluoromethoxyphenyl)-3-(4-nitrophenyl)-1H-[1,2,4]triazole. A solution of NBS (0.70 g, 3.9 mmol) in 25 mL of CH2Cl2 was stirred under nitrogen at 0° C. while dimethyl sulfide (0.40 g, 6.5 mmol) was added via syringe. The solution, which forms a white solid, was then cooled to −20° C., and N-(4-nitrobenzylidene)-N′-(4-trifluoromethoxyphenyl)-hydrazine (0.70 g, 2.15 mmol) in 10 mL of DCM was added. The solution was allowed to warm to ambient temperature and stirred an additional 2 h. The resulting orange solution was then diluted with 25 mL of DCM and washed with water and brine before drying and concentrating. The resulting orange solid hydrazonyl bromide (0.9 g) was then treated directly with tetrazole (154 mg, 2.2 mmol) and triethylamine (280 μL, 0.23 mmol) in 5 mL of absolute EtOH. The resulting orange-brown solution was heated at reflux for 2 h. TLC showed that the initial bromide was first converted into two yellow intermediates, which were replaced by a single, colorless, spot. The orange solution was then concentrated and purified by chromatography (2:1:2 Hexane/EtOAc/DCM), yielding 0.30 g of the title compound as a light yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.68 (s, 1H), 8.40 (d, J=5 Hz, 2H), 8.35 (d, J=5 Hz, 2H), 7.85 (d, J=8 Hz, 2H), 7.42 (d, J=8 Hz, 2H); EIMS 350 (M+, 100), 299 (57); mp 147° C.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][CH2:7][C:8]2([C:11]([CH3:16])([CH3:15])[CH:12]([CH3:14])[CH3:13])[CH2:10][O:9]2)=[CH:4][CH:3]=1.C([O-])CCC.[Na+].[NH:25]1[CH:29]=[N:28][CH:27]=[N:26]1>C(O)CCC>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][CH2:7][C:8]([OH:9])([C:11]([CH3:16])([CH3:15])[CH:12]([CH3:14])[CH3:13])[CH2:10][N:25]2[CH:29]=[N:28][CH:27]=[N:26]2)=[CH:4][CH:3]=1
Reactant: c1nc[nH]n1
Reactant: CC(C)C(C)(C)C1(COc2ccc(Cl)cc2)CO1
Agent: CCCC[O-]
Agent: [Na+]
Solvent: CCCCO
Product: CC(C)C(C)(C)C(O)(COc1ccc(Cl)cc1)Cn1cncn1
Yield: 36.8 %

Procedure:
376 g of crude 2-(4-chlorophenoxymethyl)-2-(1,1,2-trimethylpropyl)-oxirane dissolved in 400 ml of n-butanol are added dropwise to a boiling solution of 13.4 g (0.14 mol) of sodium butanolate and 97 g (1.4 mols of 1,2,4-triazole in 400 ml of n-butanol in 1.5 hours. After boiling under reflux for 22 hours, the solvent is removed by distillation under reduced pressure and 500 ml of dichloromethane are added to the residue. Precipitated 2-(4-chlorophenoxymethyl)-1-(1,2,4-triazol-4-yl)-3,3,4-trimethylpentan-2-ol (15 g; melting point 173°-174° C.) is filtered off from the mixture, the filtrate is washed twice with 250 ml of water each time and dried over anhydrous sodium sulphate and the solvent is removed by distillation. The residue is chromatographed on silica gel using trichloromethane as eluant. 174 g of 2-(4-chlorophenoxymethyl)-1-(1,2,4-triazol-1-yl)-3,3,4-trimethylpentan-2-ol are thus obtained in the form of colorless crystals of melting point 59°-60° C.
Reaction SMILES: [N:1]1([C:17]([O:19][CH2:20][CH:21]2[C:33]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:27]3[C:22]2=[CH:23][CH:24]=[CH:25][CH:26]=3)=[O:18])[CH2:5][CH2:4][CH2:3][C@H:2]1[C:6]([O:8][CH2:9][C:10]([O:12]C(C)(C)C)=[O:11])=[O:7].C([SiH](C(C)C)C(C)C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH:23]1[C:22]2[CH:21]([CH2:20][O:19][C:17]([N:1]3[CH2:5][CH2:4][CH2:3][C@H:2]3[C:6]([O:8][CH2:9][C:10]([OH:12])=[O:11])=[O:7])=[O:18])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]=2[CH:26]=[CH:25][CH:24]=1
Reactant: CC(C)(C)OC(=O)COC(=O)[C@@H]1CCCN1C(=O)OCC1c2ccccc2-c2ccccc21
Agent: CC(C)[SiH](C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)COC(=O)[C@@H]1CCCN1C(=O)OCC1c2ccccc2-c2ccccc21
Temperature: 25 °C
Yield: 100 %

Procedure:
A solution of (S)-1-((9H-fluoren-9-yl)methyl) 2-(2-(tert-butoxy)-2-oxoethyl) pyrrolidine-1,2-dicarboxylate (Fmoc-Pro-HOGly-OtBu) (Compound SP631) (6.40 g, 14.2 mmol) in methylene chloride (29 mL) was mixed with triisopropylsilane (7.29 mL, 35.4 mmol) and trifluoroacetic acid (14.2 mL, 184 mmol) with stirring at room temperature, and the reaction mixture was stirred at room temperature for 16 hours. The reaction solution was concentrated under reduced pressure, and the resulting residue was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution) to afford (S)-2-((1-(((9H-fluoren-9-yl)methoxy)carbonyl)pyrrolidin-2-carbonyl)oxy)acetic acid (Fmoc-Pro-HOGly-OH) (Compound SP632) (5.6 g, 14.2 mmol, 100%).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[CH:3]=1.[N:21]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1[C:27](OC)=[O:28].CO[Na].CO.Cl>O.C(#N)C>[C:19]([C:4]1[CH:3]=[C:2]([NH:1][C:27]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][N:21]=2)=[O:28])[N:6]([C:7]2[C:8]([Cl:18])=[CH:9][C:10]([C:14]([F:16])([F:15])[F:17])=[CH:11][C:12]=2[Cl:13])[N:5]=1)#[N:20]
Reactant: N#Cc1cc(N)n(-c2c(Cl)cc(C(F)(F)F)cc2Cl)n1
Reactant: COC(=O)c1cnccn1
Agent: CO[Na]
Agent: Cl
Solvent: CC#N
Solvent: CO
Solvent: O
Product: N#Cc1cc(NC(=O)c2cnccn2)n(-c2c(Cl)cc(C(F)(F)F)cc2Cl)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 73.2 %

Procedure:
Into a mixture of 0.5 g (1.6 mmol) of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole-3-carbonitrile, 0.24 g (1.7 mmol) of methyl pyrazinecarboxylate, and 0.5 ml of acetonitrile was gradually added 0.3 g (1.6 mmol) of 28% CH3ONa/CH3OH at room temperature. After 2 hours of stirring at room temperature, 5 ml of water and then concentrated hydrochloric acid were added thereto to make the mixture pH 2, whereby crystals were precipitated. Thereto was added 10 ml of ethyl acetate, followed by extraction. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. After removal of the sodium sulfate by filtration, the layer was concentrated and the resulting crystals were filtrated. The crystals were washed with a small amount of hexane and ethyl acetate and the dried to obtain 0.5 g (yield 77%) of N-[3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole-5-yl]pyrazine-2-carboxamide.
Reaction SMILES: [C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1Cl)=[CH:13][CH:12]=[CH:11][C:10]=2[CH3:17])(=[O:5])[CH2:2][CH2:3][CH3:4].[CH2:18]([C:20]1[CH:26]=[CH:25][CH:24]=[CH:23][C:21]=1[NH2:22])[CH3:19]>O1CCOCC1>[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:22][C:21]1[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=1[CH2:18][CH3:19])=[CH:13][CH:12]=[CH:11][C:10]=2[CH3:17])(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: CCc1ccccc1N
Reactant: CCCC(=O)c1cnc2c(C)cccc2c1Cl
Solvent: C1COCCO1
Product: CCCC(=O)c1cnc2c(C)cccc2c1Nc1ccccc1CC
Yield: 71.6 %

Procedure:
3-Butyryl-4-chloro-8-methylquinoline (2.48 g, 10 mmol), 2-ethylaniline (1.85 ml, 15 mmol) and 1,4-dioxan (10 ml) were stirred at room temperature overnight then heated at reflux for 30 minutes. The solvent was evaporated, the residue converted to free base and recrystallised from aqueous ethanol to give 3-butyryl-4-(2-ethylphenylamino)-8-methylquinoline (2.38 g), m.p. 117°-119°.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7].[C:8]1(=[O:18])[NH:12][C:11](=[O:13])[C:10]2=[CH:14][CH:15]=[CH:16][CH:17]=[C:9]12.[K].O>CS(C)=O>[CH2:2]([N:12]1[C:11](=[O:13])[C:10]2=[CH:14][CH:15]=[CH:16][CH:17]=[C:9]2[C:8]1=[O:18])[CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7]
Reactant: C=CCCCCBr
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Solvent: CS(C)=O
Product: C=CCCCCN1C(=O)c2ccccc2C1=O
Reaction time: 8 h
Yield: 100.3 %

Procedure:
This example illustrates a synthesis of N-(5,6-Oxidohexyl)phthalimide (inventive compound no. 1103). 1-bromo-5-hexene (6.52 g, 40 mmol) was added to a potassium phthalimide (7.4 g, 40 mmol) suspension in 50 mL of dimethyl sulfoxide and stirred overnight. After 12 hours of stirring at room temperature, the reaction was poured into a separatory funnel containing 300 mL of water and extracted with dichloromethane (5×200 mL). The organic extracts were combined, washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product obtained was further purified by flash chromatography over silica gel (eluant: 10% acetone/hexane) to yield 9.2 g (100% yield) of N-(5-Hexenyl)phthalimide (inventive compound no. 1101).