Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:11][CH:10]=2)O1.[NH2:27][C:28]1[N:33]=[CH:32][N:31]=[C:30]2[N:34]([CH:38]3[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH2:39]3)[N:35]=[C:36](I)[C:29]=12.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[NH2:27][C:28]1[N:33]=[CH:32][N:31]=[C:30]2[N:34]([CH:38]3[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH2:39]3)[N:35]=[C:36]([C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:16]([O:17][CH2:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:25])=[CH:13][CH:14]=3)[C:29]=12
Reactant: CC(C)(C)OC(=O)N1CCC(n2nc(I)c3c(N)ncnc32)CC1
Reactant: CC1(C)OB(c2ccc(NC(=O)OCc3ccccc3)cc2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(n2nc(-c3ccc(NC(=O)OCc4ccccc4)cc3)c3c(N)ncnc32)CC1
Temperature: 25 °C
Yield: 82.7 %

Procedure:
A mixture of benzyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (9.54 g, 0.027 mol), tert-butyl 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (10.0 g, 0.0225 mol), tetrakis-(triphenylphosphine)palladium (1.56 g, 0.00135 mol) and sodium carbonate (5.97 g, 0.0563 mol) was heated in a mixture of ethylene glycol dimethyl ether (120 mL) and water (60 mL) at 80° C. for 16 hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and solvents were removed under the reduced pressure. The residue was partitioned between water (150 mL) and dichloromethane (150 mL); the organic phase was washed with brine, dried with magnesium sulfate and concentrated under reduced pressure. The residue was triturated in diethyl ether and the precipitate was collected by filtration and dried to yield tert-butyl 4-[4-amino-3-(4-[(benzyloxy)carbonyl]aminophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (10.1 g, 0.0186 mol) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH:11](C(OCC)=O)[C:12]([O:14]CC)=[O:13].[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH2:11][C:12]([OH:14])=[O:13]
Reactant: CCOC(=O)C(C(=O)OCC)c1ccc([N+](=O)[O-])cc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)Cc1ccc([N+](=O)[O-])cc1Cl
Temperature: 50 °C
Reaction time: 1 h
Yield: 86.6 %

Procedure:
To a solution of diethyl 2-(2-chloro-4-nitrophenyl)malonate (step 1, 7.6 g, 24.2 mmol) in methanol (18 ml) was added 6M-NaOH (12 ml) and stirred for 1 h at 50° C. The reaction was quenched by the addition of saturated citric acid aqueous solution (16 ml) and water. The organic layer was extracted with ethyl acetate (2×50 ml), washed with brine, dried (MgSO4) and concentrated to give 4.52 g (87%) of title compound as light yellow solid.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([O:25][CH:26]1[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]1)[C:11]1[CH:12]=[C:13](OS(C(F)(F)F)(=O)=O)[CH:14]=[CH:15][CH:16]=1.[CH2:33]([Mg]Cl)[CH2:34][CH2:35][CH3:36]>O1CCCC1.CN1CCCC1=O.C(OCC)C>[CH2:33]([C:13]1[CH:12]=[C:11]([CH:10]([O:25][CH:26]2[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)[C:2]2[S:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[CH:16]=[CH:15][CH:14]=1)[CH2:34][CH2:35][CH3:36]
Reactant: CCCC[Mg]Cl
Reactant: CN1CCC(OC(c2cccc(OS(=O)(=O)C(F)(F)F)c2)c2nc3ccccc3s2)CC1
Solvent: C1CCOC1
Solvent: CN1CCCC1=O
Solvent: CCOCC
Product: CCCCc1cccc(C(OC2CCN(C)CC2)c2nc3ccccc3s2)c1
Temperature: 0 °C
Reaction time: 0.42 h

Procedure:
To a mixture of trifluoromethanesulfonic acid 3-[benzothiazol-2-yl(1-methylpiperidin-4-yloxy)methyl]phenyl ester (110 mg) and ferric acetylacetonate (4 mg) in a mixture of tetrahydrofurane (4.5 mL) and N-methylpyrrolidone (0.25 mL) cooled at 0° C. is added a 2M solution of butylmagnesium chloride in tetrahydrofurane (150 μL). The mixture is stirred at room temperature for 25 min, then warmed at 30° C. for 15 min. A second addition of butylmagnesium chloride in tetrahydrofurane (150 μL) is performed. The mixture is then diluted with diethyl ether and quenched with 0.5N hydrochloric solution. The aqueous phase is extracted with diethyl ether, then ethyl acetate. Organic phases are pooled, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography (gradient heptane/ethyl acetate from 99/1 to 90/10). The product is then refluxed in methanol and concentrated to give 2-[(3-butylphenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole.
Reaction SMILES: ClC1C=C(OC2C(C(N3C4C(=CC=CC=4)N(C4CC4)CC3)=O)=CC=CN=2)C(Cl)=CC=1C=CC(O)=O.[Cl:36][C:37]1[CH:42]=[C:41]([O:43][C:44]2[C:49]([C:50]([N:52]3[C:61]4[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=4)[N:55]([CH:62]4[CH2:64][CH2:63]4)[CH2:54][CH2:53]3)=[O:51])=[CH:48][CH:47]=[CH:46][N:45]=2)[C:40]([Cl:65])=[CH:39][C:38]=1[CH:66]=[CH:67][CH2:68][C:69]([OH:71])=[O:70]>>[Cl:36][C:37]1[CH:42]=[C:41]([O:43][C:44]2[C:49]([C:50]([N:52]3[C:61]4[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=4)[N:55]([CH:62]4[CH2:63][CH2:64]4)[CH2:54][CH2:53]3)=[O:51])=[CH:48][CH:47]=[CH:46][N:45]=2)[C:40]([Cl:65])=[CH:39][C:38]=1[CH2:66][CH2:67][CH2:68][C:69]([OH:71])=[O:70]
Reactant: O=C(O)CC=Cc1cc(Cl)c(Oc2ncccc2C(=O)N2CCN(C3CC3)c3ccccc32)cc1Cl
Agent: O=C(O)C=Cc1cc(Cl)c(Oc2ncccc2C(=O)N2CCN(C3CC3)c3ccccc32)cc1Cl
Product: O=C(O)CCCc1cc(Cl)c(Oc2ncccc2C(=O)N2CCN(C3CC3)c3ccccc32)cc1Cl

Procedure:
The title compound was prepared in analogy to Example 173 replacing 3-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-acrylic acid with 4-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-but-3-enoic acid (Example 175). MS (ISP): 526.3 [M+H]+.
Reaction SMILES: [O:1]1[C:3]23[C@:16]([CH3:21])([CH2:17][CH2:18][C:19](=[O:20])[CH:2]12)[C@@H:15]1[C@H:6]([C@H:7]2[C@@:11]([CH2:13][CH2:14]1)([CH3:12])[C:10](=[O:22])[CH2:9][CH2:8]2)[CH2:5][C:4]3=[CH2:23].[OH-].[Na+].[CH3:26]O>>[CH3:26][O:1][C:2]1[C:19](=[O:20])[CH2:18][CH2:17][C@@:16]2([CH3:21])[C:3]=1[C:4](=[CH2:23])[CH2:5][C@@H:6]1[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]1[CH2:8][CH2:9][C:10]2=[O:22]
Reactant: CO
Reactant: C=C1C[C@H]2[C@@H]3CCC(=O)[C@@]3(C)CC[C@@H]2[C@@]2(C)CCC(=O)C3OC132
Agent: [Na+]
Agent: [OH-]
Product: C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)CCC(=O)C(OC)=C12
Temperature: 25 °C
Reaction time: 8 h
Yield: 75 %

Procedure:
To a stirred suspension of 4,5-epoxy-6-methylenandrostane-3,17-dione (0.630 g, 2 mmole) in methanol (63 ml) is added a 4N sodium hydroxide aqueous solution (6.3 ml). The resulting mixture is refluxed for 1 hr, cooled to room temperature, evaporated in vacuo, taken up with water, neutralised with a 37% hydrochloric acid solution and kept at 0°-5° C. overnight. The resulting precipitate is filtered off, washed with water, dried and purified by flash column chromatography on silica gel eluting with n-hexane: ethyl acetate 60:40. There are obtained 0.530 g (75% yield) of the title compound, m.p. 196°-198° C.
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:4]=1[O:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1.[B:17](OC)([O:20]C)[O:18]C>>[F:9][C:6]1[CH:7]=[CH:8][C:3]([B:17]([OH:20])[OH:18])=[C:4]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:5]=1
Reactant: Fc1ccc(Br)c(OC2CCCCO2)c1
Reactant: COB(OC)OC
Agent: [Mg]
Product: OB(O)c1ccc(F)cc1OC1CCCCO1

Procedure:
Procedure analogous to Example 6. Use of 48.6 g (2.00 mol) of magnesium, 510 g (1.85 mol) of 2-bromo-5-fluoro-1-(tetrahydropyran-2-yloxy)benzene and 241.6 ml (2.00 mol) of trimethyl borate. The yield was 434.5 g (1.81 mol), and the product was obtained as a waxy solid which contained varying proportions of boronic anhydrides and borinic acids and was used in the following stage without further purification.
Reaction SMILES: C(N(CC)C(C1C=C(C2C=NN(CCCO)C=2)C=CC=1NC1C(C(F)(F)F)=CN=C(NC2C=CC(CP(=O)(O)OCC)=CC=2OC)N=1)=O)C.[F:50][C:51]1[CH:52]=[C:53]([CH:63]=[CH:64][C:65]=1[NH:66][C:67]1[N:72]=[C:71]([NH:73][C:74]2[C:75]([C:90](=[O:93])[NH:91][CH3:92])=[N:76][C:77]([C:80]3[CH:81]=[N:82][N:83]([CH2:85][CH2:86][CH2:87][CH2:88][OH:89])[CH:84]=3)=[CH:78][CH:79]=2)[C:70]([C:94]([F:97])([F:96])[F:95])=[CH:69][N:68]=1)[CH2:54][P:55](=[O:62])([O:59]CC)[O:56][CH2:57][CH3:58]>>[F:50][C:51]1[CH:52]=[C:53]([CH:63]=[CH:64][C:65]=1[NH:66][C:67]1[N:72]=[C:71]([NH:73][C:74]2[C:75]([C:90](=[O:93])[NH:91][CH3:92])=[N:76][C:77]([C:80]3[CH:81]=[N:82][N:83]([CH2:85][CH2:86][CH2:87][CH2:88][OH:89])[CH:84]=3)=[CH:78][CH:79]=2)[C:70]([C:94]([F:97])([F:95])[F:96])=[CH:69][N:68]=1)[CH2:54][P:55](=[O:59])([OH:62])[O:56][CH2:57][CH3:58]
Reactant: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(-c4cnn(CCCCO)c4)nc3C(=O)NC)n2)c(F)c1)OCC
Agent: CCOP(=O)(O)Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(-c4cnn(CCCO)c4)cc3C(=O)N(CC)CC)n2)c(OC)c1
Product: CCOP(=O)(O)Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(-c4cnn(CCCCO)c4)nc3C(=O)NC)n2)c(F)c1
Yield: 90.3 %

Procedure:
Prepared analogously to Compound 3A using diethyl (3-fluoro-4-{[4-({6-[1-(4-hydroxybutyl)-1H-pyrazol-4-yl]-2-(methylcarbamoyl)pyridin-3-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (Compound 23B, 133 mg, 191 μmol) to afford 115 mg of the title compound (90%). 1H NMR (400 MHz, CD3OD) δ=8.98-9.08 (m, 1H), 8.56 (s, 1H), 8.32 (s, 1H), 8.23 (s, 1H), 7.71 (d, J=8.8 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 7.26 (d, J=11.9 Hz, 1H), 7.18 (d, J=8.1 Hz, 1H), 4.24 (t, J=7.1 Hz, 2H), 3.88 (quin, J=7.0 Hz, 2H), 3.60 (t, J=6.4 Hz, 2H), 3.01-3.10 (m, 2H), 2.96-3.00 (m, 3H), 1.93-2.03 (m, 2H), 1.50-2.06 (m, 2H), 1.14 (t, J=7.07 Hz, 3H). MS (ESI): m/z=667.69 [M+H]+. UPLC: tR=1.13 min (UPLC-SQD: analytical—2 min).
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH2:10].S(Cl)([Cl:23])=O>C1(C)C=CC=CC=1>[CH:1]([O:11][C:12]1[CH:20]=[CH:19][C:15]([C:16]([Cl:23])=[O:17])=[CH:14][CH:13]=1)=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: C=CCCCCCCCCOc1ccc(C(=O)O)cc1
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: CCCCCCCCC=COc1ccc(C(=O)Cl)cc1
Reaction time: 7 h

Procedure:
To 2.8 g of p-(9-decenyloxy)benzoic acid prepared in the same manner as in 9.(2) in Example 9 added was toluene, and the resulting mixture was cooled in an ice bath. 5.0 g of thionyl chloride was then added dropwise to the toluene solution. Reaction was then carried out for 7 hours at 80° C. After conclusion of the reaction, the reaction solution was concentrated under reduced pressure, to obtain crude p-decenyloxybenzoyl chloride. 1.6 g of the hydroxy compound obtained in 17.(1) and 3.3 g of pyridine were dissolved in toluene, and the resulting toluene solution was cooled in an ice bath. A toluene solution containing the above crude p-decenyloxybenzoyl chloride was added dropwise into the toluene solution. Subsequently, reaction was carried out for 5 hours at 50° C. After conclusion of the reaction, the reaction solution was washed with water and dried over magnesium sulfate, and the solvent was distilled out under reduced pressure. The residue was purified by column chromatography, to obtain 2.0 g of the objective alkene compound. (Yield: 69%)
Reaction SMILES: COC1C=CC(C[NH:8][C:9]2[O:10][C:11]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[N:19]([S:23]([C:26]3[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=3)(=[O:25])=[O:24])[CH:18]=[C:17]4[C:33]3[CH:38]=[N:37][CH:36]=[C:35]([N:39]4[CH2:44][CH2:43][CH2:42][CH2:41][CH:40]4[CH3:45])[N:34]=3)=[N:12][N:13]=2)=CC=1>C(O)(C(F)(F)F)=O>[CH3:45][CH:40]1[CH2:41][CH2:42][CH2:43][CH2:44][N:39]1[C:35]1[N:34]=[C:33]([C:17]2[C:16]3[C:20](=[CH:21][CH:22]=[C:14]([C:11]4[O:10][C:9]([NH2:8])=[N:13][N:12]=4)[CH:15]=3)[N:19]([S:23]([C:26]3[CH:27]=[CH:28][C:29]([CH3:30])=[CH:31][CH:32]=3)(=[O:24])=[O:25])[CH:18]=2)[CH:38]=[N:37][CH:36]=1
Reactant: COc1ccc(CNc2nnc(-c3ccc4c(c3)c(-c3cncc(N5CCCCC5C)n3)cn4S(=O)(=O)c3ccc(C)cc3)o2)cc1
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccc(S(=O)(=O)n2cc(-c3cncc(N4CCCCC4C)n3)c3cc(-c4nnc(N)o4)ccc32)cc1
Temperature: 120 °C

Procedure:
N-(4-Methoxybenzyl)-5-(3-(6-(2-methylpiperidin-1-yl)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (177 mg, 0.272 mmol) was weighed into a 5 mL glass microwave tube. The material was dissolved in TFA (1.5 mL) (Aldrich). The tube was sealed and the solution was heated at 120° C. for 10 min in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden). The excess TFA was removed in vacuo, the crude residue was treated with 1N NaOH and extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated. The material was used in the next step without purification. MS (ESI, pos. ion) m/z 530.0 (M+1).
Reaction SMILES: C1C(CC2C=CC(N=C=O)=CC=2)=CC=C(N=C=O)C=1.[N-]=[C:21]=[O:22].[N-]=[C:24]=[O:25].[O:26]=[C:27]1CC(C)(C)[CH2:30][C:29](C)=[CH:28]1>>[CH2:27]([C:28]([CH2:21][OH:22])([CH2:24][OH:25])[CH2:29][CH3:30])[OH:26]
Reactant: CC1=CC(=O)CC(C)(C)C1
Reactant: [N-]=C=O
Agent: O=C=Nc1ccc(Cc2ccc(N=C=O)cc2)cc1
Product: CCC(CO)(CO)CO
Temperature: 80 °C

Procedure:
8.25 val of 4,4'-diphenylmethane-diisocyanate, which contains its own dimers and trimers (Isonate 143 L), are introduced into a reactor together with 2.5 val of isophorone-diisocyanate and then heated to an internal temperature of 80° C. while stirring and leading in nitrogen to provide an inert atmosphere, the reaction continuing until a clear solution is present. In the meantime, in a second reactor, a solution of 0.9 val of castor oil and 1.3 val of trimethylolpropane is produced within about 1 hour at 90° C. The trimethylolpropane/castor oil solution after cooling to 70° C. is then added over a one hour period to the isocyanate solution preheated to 80° C. The temperature which increases as a result of the exothermic reaction may reach a maximum of 100° C. However, the reaction temperature should be regulated by cooling so as not to exceed 90° C. The reaction mixture is caused to react for a period of 2 hours, up until the mixture has reached an isocyanate content of 19.3 to 19.7 percent by weight.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:33])[CH2:5][NH:6][C:7]([N:9]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:21][CH:20]=1)[NH:10]C(OC(C)(C)C)=O)=[O:8])[CH3:2].C(C1C=CC(N(C)C(=O)OC(C)(C)C)=CC=1)CCCCCCC>>[CH2:25]([C:22]1[CH:23]=[CH:24][C:19]([CH2:18][N:9]([C:7]([NH:6][CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:33])=[O:8])[NH2:10])=[CH:20][CH:21]=1)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCCCc1ccc(CN(NC(=O)OC(C)(C)C)C(=O)NCC(=O)OCC)cc1
Agent: CCCCCCCCc1ccc(N(C)C(=O)OC(C)(C)C)cc1
Product: CCCCCCCCc1ccc(CN(N)C(=O)NCC(=O)OCC)cc1
Yield: 89 %

Procedure:
When the product of Step C was substituted for tert-butyl 4-n-octylphenyl(methyl)carbamate in Example 12, Step B, the identical process afforded the title compound in 89% yield, as a creamy solid, which was used in the next step without further purification. 1H-NMR (CDCl3) 7.15 (m, 4H); 6.84 (broad m, 1H); 4.66 (s, 2H); 4.2 (q, 2H, J=7.14 Hz); 4.02 (d, 2H, J=5.8 Hz); 3.42 (bs, 2H); 2.57 (t, 2H, J=7.9 Hz); 1.57 (m, 2H); 1.27 (m, 13H); 0.86 (t, 3H, J=6.9 Hz).
Reaction SMILES: [C:1]1([S:7]([C:10]2[C:11]([S:23][CH3:24])=[N:12][N:13]3[C:18](Cl)=[CH:17][C:16]([CH:20]4[CH2:22][CH2:21]4)=[N:15][C:14]=23)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH3:25]>CO>[C:1]1([S:7]([C:10]2[C:11]([S:23][CH3:24])=[N:12][N:13]3[C:18]([NH2:25])=[CH:17][C:16]([CH:20]4[CH2:22][CH2:21]4)=[N:15][C:14]=23)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CSc1nn2c(Cl)cc(C3CC3)nc2c1S(=O)(=O)c1ccccc1
Reactant: N
Solvent: CO
Product: CSc1nn2c(N)cc(C3CC3)nc2c1S(=O)(=O)c1ccccc1

Procedure:
In an analogous manner to that described in Example 4, from 3-benzenesulphonyl-7-chloro-5-cyclopropyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidine and NH3 in MeOH there was obtained 3-benzenesulphonyl-5-cyclopropyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidine-7-ylamine as colorless crystals, m.p.>230°.
Reaction SMILES: Cl[CH2:2][C:3]1([CH2:7]Cl)[CH2:6][O:5][CH2:4]1.[F:9][C:10]([F:20])([C:13]([F:19])([F:18])[C:14]([F:17])([F:16])[F:15])[CH2:11][OH:12].[H-].[Na+]>CN(C=O)C>[F:9][C:10]([F:20])([C:13]([F:18])([F:19])[C:14]([F:15])([F:16])[F:17])[CH2:11][O:12][CH2:2][C:3]1([CH2:7][O:12][CH2:11][C:10]([F:9])([F:20])[C:13]([F:18])([F:19])[C:14]([F:15])([F:17])[F:16])[CH2:6][O:5][CH2:4]1
Reactant: ClCC1(CCl)COC1
Reactant: OCC(F)(F)C(F)(F)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: FC(F)(F)C(F)(F)C(F)(F)COCC1(COCC(F)(F)C(F)(F)C(F)(F)F)COC1
Yield: 70.5 %

Procedure:
In a manner similar to that described above, 3,3-bis(chloromethyl) oxetane (155 g, 1 mole) was reacted with 2,2,3,3,4,4,4-heptafluorobutan-1ol (402 g, 2.01 moles) in DMF (2 L) in the presence of sodium hydride (100 g of 50% dispersion in mineral oil, 2.3 moles) at 85° C. for 16 h to give 340 g (70%) of 3,3-bis(2,2,3,3,4,4,4-heptafluorobutoxymethyl) oxetane, a clear, colorless liquid. Glc analysis revealed the purity of this material to be in excess of 99%: BP=70°-72° C./1.0-1.3 mm-hG; 1H NMR (CDCl3) δ 4.44 (s, 4H), 3.97 (t, J=13.2 Hz), 3.86 (s, 4H); 13cNMR δ 43.9, 68.1 (t), 73.5, and 75.6 (Signals from carbons bearing fluorine are not included due to the complex splitting patterns and overlap of signals); 19fNMR δ -81.6 (3 F), -121.0 (2 F) and -128.3 (2 F); Anal. Calcd for C13H12F14O3 : C, 32.4; H, 2.5. Found: C, 32.3; H, 2.3.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:11][CH3:12])[N:7]=[C:8]([NH2:10])[CH:9]=1)=[O:4].[F:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:11][CH3:12])[N:7]=[C:8]([NH:10][CH2:18][C:17]2[CH:20]=[CH:21][C:14]([F:13])=[CH:15][CH:16]=2)[CH:9]=1)=[O:4]
Reactant: O=Cc1ccc(F)cc1
Reactant: CCn1nc(N)cc1C(=O)OC
Agent: CC[SiH](CC)CC
Solvent: CC#N
Solvent: O=C(O)C(F)(F)F
Product: CCn1nc(NCc2ccc(F)cc2)cc1C(=O)OC
Temperature: 80 °C
Reaction time: 4 h

Procedure:
To 5-amino-2-ethyl-2H-pyrazole-3-carboxylic acid methyl, ester (527, 1.00 g, 5.91 mmol) in acetonitrile (27.5 mL) were added 4-fluorobenzaldehyde (528, 0.660 mL, 6.26 mmol), triethylsilane (4.77 mL, 0.0298 mol) and trifluoroacetic acid (2.38 mL, 0.0310 mol). The reaction was stirred at 80° C. for 4 hours, then concentrated, poured into aqueous potassium carbonate, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give a white solid (529, 1.00 g, 61%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH:9]=[C:10]2[CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[CH:5][CH:4]=1.ClC1C(=O)C(=O)C(Cl)=C(Cl)C=1Cl>C(O)C>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][CH:9]=[C:10]2[CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[CH:5][CH:4]=1
Reactant: COc1ccc2c(c1)C(C1CCN(C)CC1)=CCC2
Agent: O=C1C(=O)C(Cl)=C(Cl)C(Cl)=C1Cl
Solvent: CCO
Product: COc1ccc2cccc(C3CCN(C)CC3)c2c1

Procedure:
A mixture of 11.5 g of the product from Example 15 and 23.1 g of tetrachloro-1,2-benzoquinone in solution in 600 ml of anhydrous ethyl alcohol is refluxed for 30 hours.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][N:8]2[CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]1)([O-:3])=[O:2].C(N(CC)CC)C.[C:27](OC(=O)C)(=[O:29])[CH3:28]>C(Cl)Cl>[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][N:8]2[CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][N:16]([C:27](=[O:29])[CH3:28])[CH2:15]1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cccc2c1cnn2CC1CCCNC1
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)N1CCCC(Cn2ncc3c([N+](=O)[O-])cccc32)C1
Reaction time: 1 h
Yield: 52.4 %

Procedure:
A solution of 4-nitro-1-(piperidin-3-ylmethyl)-1H-indazole (0.050 g, 0.139 mmol), triethylamine (0.097 mL, 0.699 mmol) in DCM (1 mL) was treated with acetic anhydride (0.0158 mL, 0.168 mmol) at ambient temperature and stirring continued for 1 hour. The mixture was quenched with saturated aqueous sodium bicarbonate, extracted with DCM, dried (phase separator silicone treated filter paper) and concentrated to provide 1-(3-((4-nitro-1H-indazol-1-yl)methyl)piperidin-1-yl)ethanone (0.022 g, 52% yield) as a yellow oil.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=O)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[O:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][NH:28][C:29](=[O:34])/[CH:30]=[C:31](\[NH2:33])/[CH3:32])[CH2:22][CH2:21]1>C1(C)C=CC=CC=1>[O:20]1[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][NH:28][C:29]([C:30]2[C:31]([CH3:32])=[N:33][C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:11][C:10]=2[C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)=[O:34])[CH2:24][CH2:25]1
Reactant: C/C(N)=C/C(=O)NCCN1CCOCC1
Reactant: O=C(C=Cc1cccc([N+](=O)[O-])c1)c1ccccc1
Solvent: Cc1ccccc1
Product: Cc1nc(-c2ccccc2)cc(-c2cccc([N+](=O)[O-])c2)c1C(=O)NCCN1CCOCC1
Temperature: 25 °C
Yield: 31.2 %

Procedure:
A mixture of 3-(3-nitrophenyl)-1-phenyl-2-propen-1-one (20 g) and N-(2-morpholinoethyl)-3-aminocrotonamide (21.9 g) in toluene (200 ml) was refluxed for hours. After allowing to cool at ambient temperature, the reaction mixture was concentrated in vacuo. The residue was subjected to a column chromatography on silica gel eluting with a mixture of ethyl acetate and tetrahydrofuran (100:1 V/V). The fractions containing the object compound were combined and concentrated in vacuo. The residue was recrystallized from ethyl alcohol to give 3-(2-morpholinoethylcarbamoyl)-2-methyl-4-(3-nitrophenyl)-6-phenylpyridine (11.0 g).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[N:8][OH:9])[NH2:7].[N+:10]([C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=O)=[CH:15][CH:14]=1)([O-:12])=[O:11].C>O1CCOCC1.B(F)(F)F.C(OCC)C>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:7]=[C:17]([C:16]2[CH:20]=[CH:21][C:13]([N+:10]([O-:12])=[O:11])=[CH:14][CH:15]=2)[O:9][N:8]=1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: NC(=NO)c1ccco1
Agent: C
Agent: FB(F)F
Solvent: CCOCC
Solvent: C1COCCO1
Product: O=[N+]([O-])c1ccc(-c2nc(-c3ccco3)no2)cc1
Yield: 74.6 %

Procedure:
To a solution of 2-furanamidoxime (12.6 g, 0.1 mole) and p-nitrobenzoyl chloride (18.1 g, 0.1 mole) in 500 ml of dry dioxane, 1 ml of BF3 -ethyl ether is added and the mixture is heated to reflux for 16 hours. Evaporation of the solvent in vacuo gives a light brown solid. It is decolorized with Darco (CHCl3) and crystallized from ethanol-acetonitrile to give 19.2 g (75%) of product, m.p. 168°-170°.
Reaction SMILES: [CH:1]1([C:4]2[N:9]=[C:8]([C:10]([Cl:13])([Cl:12])[Cl:11])[N:7]=[C:6](C(Cl)(Cl)Cl)[N:5]=2)[CH2:3][CH2:2]1.[NH3:18]>O1CCCC1.O>[NH2:18][C:6]1[N:5]=[C:4]([CH:1]2[CH2:2][CH2:3]2)[N:9]=[C:8]([C:10]([Cl:13])([Cl:12])[Cl:11])[N:7]=1
Reactant: ClC(Cl)(Cl)c1nc(C2CC2)nc(C(Cl)(Cl)Cl)n1
Reactant: N
Solvent: C1CCOC1
Solvent: O
Product: Nc1nc(C2CC2)nc(C(Cl)(Cl)Cl)n1

Procedure:
71.2 g of 2-cyclopropyl-4,6-bis-trichloromethyl-1,3,5-triazine are dissolved in 70 ml of tetrahydrofuran, and at room temperature are added, with stirring, 300 ml of a concentrated aqueous ammonia solution. The reaction mixture is stirred for 30 minutes; it is then diluted with water, and the formed emulsion is extracted with ether. The ether phases are collected, dried, filtered and subsequently concentrated by evaporation. The residue crystallises and there remain 48 g of the crystalline title product, m.p. 111°-114° C.