Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC1C=CC=C(F)C=1C(N=C=O)=O.Cl[C:15]1[CH:29]=[C:28]([N+]([O-])=O)[CH:27]=[CH:26][C:16]=1[O:17][C:18]1[CH:24]=[CH:23][C:21](N)=[C:20](C)[CH:19]=1>C1(C)C=CC=CC=1>[C:18]1([O:17][C:16]2[CH:15]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:19]=[CH:20][CH:21]=[CH:23][CH:24]=1
Reactant: Cc1cc(Oc2ccc([N+](=O)[O-])cc2Cl)ccc1N
Agent: O=C=NC(=O)c1c(F)cccc1F
Solvent: Cc1ccccc1
Product: c1ccc(Oc2ccccc2)cc1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A solution of 3.7 g (0.02 mole) of 2,6-difluorobenzoylisocyanate in 20 ml of toluene was added dropwise at 50° C to a solution of 5.6 g (0.02 mole) of 4-(2'-chloro-4'-nitrophenoxy)-2-methylaniline in 100 ml of toluene. The batch was stirred for 1 hour at 60° C. The substance which separated out was filtered off after cooling the reaction mixture to 20° C and was washed with toluene and petroleum ether. After drying, 7 g (75% of theory) of 2-chloro-4-nitro-3'-methyl-4'-[N-(N'-2,6-difluorobenzoyl))-ureido]-diphenyl ether of melting point 190° C were obtained.
Reaction SMILES: [Na].[OH:2][C:3]1[C:8]([CH2:9][CH2:10][CH3:11])=[C:7]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[NH:24][N:23]=[N:22][N:21]=3)=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]=1[C:25](=[O:27])[CH3:26].[Br:28][CH2:29][CH2:30][CH2:31]Br.CCC(C)=O.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C>[C:25]([C:4]1[CH:5]=[CH:6][C:7]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:21]=[N:22][N:23]([CH2:31][CH2:30][CH2:29][Br:28])[N:24]=3)=[CH:16][CH:15]=2)=[C:8]([CH2:9][CH2:10][CH3:11])[C:3]=1[OH:2])(=[O:27])[CH3:26]
Reactant: BrCCCBr
Reactant: CCCc1c(COc2ccc(-c3nnn[nH]3)cc2)ccc(C(C)=O)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na]
Solvent: CCC(C)=O
Solvent: CCOC(C)=O
Product: CCCc1c(COc2ccc(-c3nnn(CCCBr)n3)cc2)ccc(C(C)=O)c1O
Temperature: 25 °C
Reaction time: 8 h
Yield: 81.3 %

Procedure:
1-[2-Hydroxy-3-propyl-4-((4-(1H-tetrazol-5-yl)phenoxy)methyl)phenyl]ethanone sodium salt (5 g, 0.013 mol), 1,3-dibromopropane (3.5 g, 0.18 mol), and MEK (50 ml) were combined potassium carbonate (4.15 g, 0.025 mol) potassium was added and the reaction mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure. The volume of the concentrate was doubled by the addition of water and the resultant solution was extracted with ethyl acetate (3×). The ethylacetate layers were combined, washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed by HPLC (preparatory-scale, silica gel column, eluted with a mixture of 9:1 toluene:ethyl acetate) to yield 5.0 g, 82% yield of the title product: n.m.r. (300 MHz CDCl3) δ: 1.0 (t, 3H); 1.6 (m, 2H); 2.6 (s and t, 5H); 2.7 (t, 2H); 3.5 (t, 2 H); 4.8 (t, 2H); 5.15 (s, 2H); 7.1 (d, 2H); d, 1H); 7.6 (d, 1H); 8.1 (d, 2H); 12.7 (s, 1H).
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[C:5]([C:7]([OH:9])=[O:8])[N:6]=1.F[C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][C:12]=1[F:19].C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[C:15]([C:14]1[CH:17]=[CH:18][C:11]([N:3]2[CH:4]=[C:5]([C:7]([OH:9])=[O:8])[N:6]=[C:2]2[CH3:1])=[C:12]([F:19])[CH:13]=1)#[N:16]
Reactant: Cc1nc(C(=O)O)c[nH]1
Reactant: N#Cc1ccc(F)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1nc(C(=O)O)cn1-c1ccc(C#N)cc1F
Temperature: 100 °C

Procedure:
A mixture of 2-methyl-1H-imidazole-4-carboxylic acid (400 mg), 4-fluoro-3-fluorobenzonitrile (0.53 g), and K2CO3 (1.3 g) in N,N-dimethylformamide (6 mL) is heated to 100° C. for 30 minutes in a microwave. The crude product is purified by HPLC. LC (method 20): tR=1.24 min; Mass spectrum (APCI): m/z=246 [M+H]+.
Reaction SMILES: [C:1]([OH:16])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[OH-].[Na+:18].[Cl-].[Na+]>O>[C:1]([O-:16])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[Na+:18]
Reactant: CCCCCCCCCCCCCC(=O)O
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCCCCCCCCC(=O)[O-]

Procedure:
Melt Myristic acid at 65° C. Separately heat water, sodium hydroxide and sodium chloride at 80° C. When at temperature, add to Myristic acid to form sodium Myristate, mix gently until reacted. Add surfactants (Cocoamidopropyl Betaine and Sodium Lauryl Sarcosinate) and mix until dissolved. Add glycerine and SDBAC & mix for 10 minutes. Add petrolatum and mix at low speed to avoid shearing into small particle size. Allow to cool & set. Re-melt temperature is around 70° C.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[NH:10][CH2:11][CH2:12][CH3:13].ClCCl.[C:17](Cl)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:1][CH:2]1[N:10]([CH2:11][CH2:12][CH3:13])[C:17](=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CCCNC1Cc2ccccc2C1
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Product: CCCN(C(=O)c1ccccc1)C1Cc2ccccc2C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 98.9 %

Procedure:
To a stirred solution of Indan-2-yl-propyl-amine (20.0 g, 114 mmol) in dichloro methane (200 mL) triethyl amine (17.4 mL, 125 mmol) was added. To this solution was then dropwise added benzoyl chloride (17.6 g, 125 mmol), followed by stirring at ambient temperature for 2 hours. The reaction was finally quenched by addition of dilute hydrochloric acid (50 mL, 10% HCl). The organic layer was separated, washed with water and dried over magnesium sulfate. Evaporation of the solvent yielded 31.5 g (99%) of the title compound as a dark oil.:
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[C:14]1[N:18]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[N:17]=[CH:16][C:15]=1[N+:27]([O-:29])=[O:28])(=O)=O.[CH:32]1(B(O)O)[CH2:34][CH2:33]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Br-].[Na+].O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([CH:32]2[CH2:34][CH2:33]2)=[C:8]([C:14]2[N:18]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[N:17]=[CH:16][C:15]=2[N+:27]([O-:29])=[O:28])[CH:9]=1
Reactant: C[Si](C)(C)CCOCn1ncc([N+](=O)[O-])c1-c1cc(Cl)ccc1OS(=O)(=O)C(F)(F)F
Reactant: OB(O)C1CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [Br-]
Solvent: O
Solvent: Cc1ccccc1
Product: C[Si](C)(C)CCOCn1ncc([N+](=O)[O-])c1-c1cc(Cl)ccc1C1CC1
Temperature: 90 °C
Yield: 53.1 %

Procedure:
To a mixture of 4-chloro-2-(4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)phenyl trifluoromethanesulfonate (72.4 mg, 0.144 mmol), cyclopropylboronic acid (55.0 mg, 0.640 mmol), tetrakis(triphenylphosphine)palladium(0) (79.2 mg, 0.685 mmol), potassium phosphate (152.7 mg, 0.7194 mmol), and sodium bromide (149.2 mg, 1.450 mmol) was added water (13.0 μL, 0.722 mmol) and toluene (3.0 mL). The reaction mixture was heated at 90° C. for 72 hours. The reaction mixture was partitioned between ethyl acetate and water, and the organic layer washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (0 to 30% ethyl acetate in heptanes) to yield 30.1 mg (53%) of 5-(5-chloro-2-cyclopropylphenyl)-4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole. LCMS (ESI) m+Na=416.2.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[O:14][C:13](=[O:15])[O:12][N:11]=1)=[O:3].O[CH2:17][CH2:18][O:19][C:20](=[O:24])[C:21]([CH3:23])=[CH2:22].N1C=CC=CC=1>O1CCOCC1>[C:20]([O:19][CH2:18][CH2:17][C:2]([O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[O:14][C:13](=[O:15])[O:12][N:11]=1)=[O:3])(=[O:24])[C:21]([CH3:23])=[CH2:22]
Reactant: C=C(C)C(=O)OCCO
Reactant: O=C(Cl)OCCCCCc1noc(=O)o1
Solvent: C1COCCO1
Solvent: c1ccncc1
Product: C=C(C)C(=O)OCCC(=O)OCCCCCc1noc(=O)o1
Yield: 95.7 %

Procedure:
In accordance with the procedure of Example 1, 35.34g (0.15 moles) 5-(chloroformyloxypentyl)-1,3,4-dioxazol-2-one is reacted with 21.47g (0.165 moles) hydroxyethylmethacrylate in 75 ml 1,4-dioxane by adding 11.86g (0.15 moles) pyridine in 65 ml 1,4-dioxane over a 1 hour period at 19-21° C. After work-up, 47.30g of a slightly brown liquid is obtained which is analyzed by IR and NMR spectroscopy to be 5-[(methacryloyloxyethyl) formyloxypentyl]-1,3,4-dioxazol-2-one (yield 95.7%), having the following formula: ##STR16##
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][N:9]([CH3:11])[CH3:10])[N:3]=1.[CH3:12][N:13]([CH2:15][CH2:16][NH2:17])[CH3:14].[OH-].[Na+]>N1C=CC=CC=1>[CH3:12][N:13]([CH3:14])[CH2:15][CH2:16][NH:17][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][N:9]([CH3:11])[CH3:10])[N:3]=1
Reactant: CN(C)CCN
Reactant: CN(C)Cc1cccc(Cl)n1
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccncc1
Product: CN(C)CCNc1cccc(CN(C)C)n1
Yield: 35.4 %

Procedure:
2-Chloro-6-dimethylaminomethylpyridine (14 g., 0.0825 mole) and unsym-dimethylethylenediamine (21.8 g, 0.248 mole) in 10 ml of pyridine are heated at 180° for 8 hours in a bomb. The dark reaction mixture is stirred over 20 g of solid sodium hydroxide for 1 hour on a steam bath. Then the mixture is filtered. Distillation of the filtrate gives 6.5 g of product, b.p. 110°-11° at 0.1 mm, nD25 1.5287.
Reaction SMILES: [CH2:1]([O:33][CH:34]1[C@H:38]2[C@H:39](O)[N:40](C(OCC=C)=O)[C:41]3[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][C:42]=3[C:43](=[O:44])[N:37]2[CH2:36]/[C:35]/1=[CH:58]/[CH3:59])[CH2:2][CH2:3][CH2:4][CH2:5][O:6][CH:7]1[C@H:11]2[C@H:12](O)[N:13](C(OCC=C)=O)[C:14]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:15]=3[C:16](=[O:17])[N:10]2[CH2:9]/[C:8]/1=[CH:31]/[CH3:32].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1CCCC1.C(Cl)(Cl)Cl.CO>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:33][CH:34]1[C@@H:38]2[CH:39]=[N:40][C:41]3[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][C:42]=3[C:43](=[O:44])[N:37]2[CH2:36]/[C:35]/1=[CH:58]/[CH3:59])[CH2:2][CH2:3][CH2:4][CH2:5][O:6][CH:7]1[C@@H:11]2[CH:12]=[N:13][C:14]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:15]=3[C:16](=[O:17])[N:10]2[CH2:9]/[C:8]/1=[CH:31]/[CH3:32]
Reactant: C=CCOC(=O)N1c2ccc(OC)cc2C(=O)N2C/C(=C/C)C(OCCCCCOC3/C(=C\C)CN4C(=O)c5cc(OC)ccc5N(C(=O)OCC=C)[C@@H](O)[C@H]34)[C@H]2[C@@H]1O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCNC1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: C/C=C1/CN2C(=O)c3cc(OC)ccc3N=C[C@H]2C1OCCCCCOC1/C(=C\C)CN2C(=O)c3cc(OC)ccc3N=C[C@@H]12
Temperature: 25 °C

Procedure:
A catalytic amount of tetrakis(triphenylphosphine)palladium (14.4 mg, 12.5 μmol) was added to a stirred solution of the bis-alloc-carbinolamine 5 (200 mg, 0.25 mmol), triphenylphosphine (6.30 mg, 24.1 μmol) and pyrrolidine (33 mg, 40.1 μL 0.48 mmol) in CH2Cl2 (13 mL) under a nitrogen atmosphere. The reaction mixture was allowed to warm to room temperature and the progress of reaction monitored by TLC (95:5 v/v CHCl3/MeOH). After two and a half hours TLC revealed the reaction was complete to give a spot which fluoresced brightly under UV light. The solvent was evaporated under reduced pressure and the resulting residue subjected to flash chromatography (98:2 v/v CHCl3/MeOH) to give the bis-imine target molecule 1 as a pale orange glass which was repeatedly evaporated in vacuo with CHCl3 to provide the imine form. Yield=160 mg (Quant); [α]21D=+937° (c=0.641, CHCl3); 1H NMR (250 MHz, CDCl3) δ 7.67 (d, 2H, J=4.5 Hz), 7.50 (s, 2H) 6.80 (s, 2H), 5.63-5.55 (m, 2H), 4.38-3.96 (m, 8H), 3.94 (s, 6H), 3.86-3.80 (m, 2H), 3.20-3.03 (m, 2H), 2.90 (d, 2H, J=15.8 Hz), 2.00-1.91 (m, 4H), 1.76-1.68 (m, 8H); 13C NMR (62.9 MHz, CDCl3) δ 164.9, 163.0, 150.8, 147.8, 140.6, 132.9, 119.8, 119.3, 111.4, 110.3, 68.7, 56.1, 53.4, 48.3, 35.3, 28.6, 22.5, 14.9; MS (FAB) m/z (relative intensity) 613 ([M+H]+, 52), 443 (26), 421 (22), 329 (100), 307 (71), 242 (35), 220 (38); IR (CHCl3) 3220 (br), 2940, 2859, 1697, 1602, 1560, 1508, 1458, 1432, 1382, 1341, 1263, 1217, 1132, 1098, 1065, 1007, 875, 666 cm−1; HRMS [M+H]+ calcd for C35H41N4O6 m/z 613.3026, found (FAB) m/z 613.3047.
Reaction SMILES: CS([C:5]1[N:10]=[C:9]([C:11]2[S:12][C:13]([S:16]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)(=[O:18])=[O:17])=[CH:14][CH:15]=2)[CH:8]=[CH:7][N:6]=1)(=O)=O.[NH2:25][CH2:26][CH2:27][N:28]1[CH2:32][CH2:31][NH:30][C:29]1=[O:33].C(N(CC)CC)C>C1(C)C=CC=CC=1>[O:22]1[CH2:23][CH2:24][N:19]([S:16]([C:13]2[S:12][C:11]([C:9]3[CH:8]=[CH:7][N:6]=[C:5]([NH:25][CH2:26][CH2:27][N:28]4[CH2:32][CH2:31][NH:30][C:29]4=[O:33])[N:10]=3)=[CH:15][CH:14]=2)(=[O:18])=[O:17])[CH2:20][CH2:21]1
Reactant: NCCN1CCNC1=O
Reactant: CS(=O)(=O)c1nccc(-c2ccc(S(=O)(=O)N3CCOCC3)s2)n1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: O=C1NCCN1CCNc1nccc(-c2ccc(S(=O)(=O)N3CCOCC3)s2)n1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A mixture of 2-(methylsulfonyl)-4-(5-(morpholinosulfonyl)thiophen-2-yl)pyrimidine (100 mg, 0.26 mmol), 1-(2-aminoethyl)imidazolidin-2-one (36 mg, 0.28 mmol) and triethylamine (56 mg, 0.52 mmol) in toluene (3 mL) was refluxed for 6 h. After cooling to rt, the solvent was evaporated in vacuo and then methanol (5 mL) was added. After stirring for 15 min the solid was filtered and dried to give the title compound with a light yellow color (81 mg, 72%). MS (M+H)+ 439.
Reaction SMILES: N#N.[F:3][C:4]([C:7]1[N:8]=[C:9]([CH2:12][N:13]2[N:17]=[C:16]([N+:18]([O-])=O)[CH:15]=[N:14]2)[O:10][CH:11]=1)([F:6])[CH3:5].[NH4+].[Cl-]>CCO.O.[Fe]>[F:3][C:4]([C:7]1[N:8]=[C:9]([CH2:12][N:13]2[N:17]=[C:16]([NH2:18])[CH:15]=[N:14]2)[O:10][CH:11]=1)([F:6])[CH3:5]
Reactant: CC(F)(F)c1coc(Cn2ncc([N+](=O)[O-])n2)n1
Agent: [Fe]
Agent: N#N
Agent: [Cl-]
Solvent: O
Solvent: CCO
Product: CC(F)(F)c1coc(Cn2ncc(N)n2)n1
Temperature: 70 °C
Reaction time: 1 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a mixture of 2-[4-(1,1-difluoro-ethyl)-oxazol-2-ylmethyl]-4-nitro-2H-[1,2,3]triazole (130 mg, 0.50 mmol), iron powder (85 mg, 1.41 mmol) and NH4Cl (136 mg, 2.51 mmol) in a mixture of EtOH (2.0 mL) and water (1.0 mL) was stirred at 70° C. for 60 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 mL) was added followed by water (10 mL). The aq. layer was extracted with CH2Cl2 (2×10 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a yellow oil. LC-MS-conditions 05c: tR=0.47 min.
Reaction SMILES: [C:1]([O-:8])(=[O:7])[NH:2][NH:3][C:4]([O-:6])=[O:5].[CH2:9]=[CH:10][CH:11]=[CH2:12].[CH2:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[N:2]([C:1]([O:8][CH2:13][CH3:14])=[O:7])=[N:3][C:4]([O:6][CH2:9][CH3:10])=[O:5].[CH2:9]=[CH:10][CH:11]=[CH2:12].[CH2:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=C([O-])NNC(=O)[O-]
Agent: C=CC=C
Solvent: C=Cc1ccccc1
Product: CCOC(=O)N=NC(=O)OCC

Procedure:
This example demonostrates the preparation and evaluation of a bicarbamate-modified linear butadiene-styrene teleblock copolymer resulting from the addition reaction of diethyl azodicarboxylate with a typical linear butadiene-styrene teleblock copolymer.
Reaction SMILES: [N+:1]([C:4]1[S:8][C:7]([C:9]2[C:10]([CH3:24])=[N:11][N:12]3[C:17]([CH:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[CH:16][C:15]([CH3:23])=[N:14][C:13]=23)=[C:6]([CH3:25])[CH:5]=1)([O-])=O.[C:26](Cl)(=[O:28])[CH3:27].ClCCl>C1COCC1.[Pd]>[CH2:19]([CH:18]([C:17]1[N:12]2[N:11]=[C:10]([CH3:24])[C:9]([C:7]3[S:8][C:4]([NH:1][C:26](=[O:28])[CH3:27])=[CH:5][C:6]=3[CH3:25])=[C:13]2[N:14]=[C:15]([CH3:23])[CH:16]=1)[CH2:21][CH3:22])[CH3:20]
Reactant: CC(=O)Cl
Reactant: CCC(CC)c1cc(C)nc2c(-c3sc([N+](=O)[O-])cc3C)c(C)nn12
Agent: [Pd]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCC(CC)c1cc(C)nc2c(-c3sc(NC(C)=O)cc3C)c(C)nn12
Temperature: 25 °C
Reaction time: 3 h
Yield: 24.9 %

Procedure:
Dissolve 3-(5-nitro-3-methyl-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (0.33 g, 0.92 mmol) in THF (10 mL) with 10% palladium on carbon (0.10 g), degas with vacuum/hydrogen atmosphere flush (3×) and stir under a hydrogen atmosphere (55 psi) at room temperature for 3 h. Confirm the reaction is complete using TLC. Dilute the reaction with THF (50 mL) and filter through diatomaceous earth, followed by concentration to a crude orange oil (0.328 g). Dissolve the oil in dichloromethane (4 mL) and 1.0 M NaOH (1 mL). Add acetyl chloride (0.038 mL, 0.52 mmol) to the reaction and stir in a sealed reaction vessel at room temperature over the weekend. Dilute the reaction with dichloromethane (100 mL) and wash with water. Collect the organic phase, dry over anhydrous magnesium sulfate, filter, and concentrate to a red oil under reduced pressure. Purify the oil using flash chromatography, eluting with 100% hexane/0% (15% ethyl acetate/10% 7 N ammoniated methanol/75% hexane) to 0% hexane/100% (15% ethyl acetate/10% 7 N ammoniated methanol/75% hexane) in a step gradient of 10% increments to give a brown foam (0.048 g, 26%). ES/MS m/z 371.0 (M+1)+.
Reaction SMILES: C(O[B:4]([O:8]CC)[O:5]CC)C.Br[C:12]1[CH:13]=[N:14][CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1.C([Li])CCC.Cl.CCOC(C)=O.CCCC(C)C>C1COCC1>[F:19][C:18]([F:21])([F:20])[C:16]1[CH:17]=[C:12]([B:4]([OH:5])[OH:8])[CH:13]=[N:14][CH:15]=1
Reactant: CCOB(OCC)OCC
Reactant: FC(F)(F)c1cncc(Br)c1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCCC(C)C
Product: OB(O)c1cncc(C(F)(F)F)c1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
Triethylborate (24 ml, 139 mmol) is added to a solution of 3-bromo-5-trifluoromethyl-pyridine (30 g, 133 mmol) in THF (300 ml) and the resulting pale yellow solution is cooled to −78° C. A solution of 1.6 M n-butyl lithium in hexanes (97 ml, 139 mmol) is added via cannula dropwise over 40 minutes, keeping the temperature below −65° C. Once addition is complete, the reaction mixture is allowed to warm slowly to room temperature and stirred for 1 hour. 1M HCl (200 ml) is added and the reaction mixture stirred for 15 minutes. The layers are separated and the organic layer is washed with 1M HCl (200 ml). The aqueous layers are combined and washed with EtOAc (2×250 ml). The pH of the aqueous phase is adjusted by the addition of 2M NaOH, and extracted with EtOAc (2×250 ml). Concentration in vacuo affords a solid, which is recyrstallised from EtOAc/iso-hexane to yield the title compound as a yellow solid [M+H]+ 192.
Reaction SMILES: Cl.[C:2]([N:12]1[CH2:17][CH2:16][NH:15][CH:14]([C:18]([OH:20])=[O:19])[CH2:13]1)([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].Cl[C:22]1[C:27]([N+:28]([O-:30])=[O:29])=[CH:26][CH:25]=[CH:24][N:23]=1.C(N(CC)CC)C.Cl>O.CS(C)=O>[N+:28]([C:27]1[C:22]([N:15]2[CH2:16][CH2:17][N:12]([C:2]([O:4][CH2:5][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=3)=[O:3])[CH2:13][CH:14]2[C:18]([OH:20])=[O:19])=[N:23][CH:24]=[CH:25][CH:26]=1)([O-:30])=[O:29]
Reactant: O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1
Reactant: O=[N+]([O-])c1cccnc1Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: CS(C)=O
Product: O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1ncccc1[N+](=O)[O-]
Reaction time: 18 h

Procedure:
A solution of 6.0 g. of 4-carbobenzoxypiperazine-2-carboxylic acid hydrochloride, 3.3 g. of 2-chloro-3-nitropyridine and 15 ml. of triethyl amine in 100 ml. of dimethyl sulfoxide is heated at 60° with stirring for 18 hours. The mixture is diluted with 400 ml. of water, acidified to pH 3 with concentrated hydrochloric acid, and extracted repeatedly with ether. The combined ether extracts are dried (MgSO4) and concentrated. The residue is crystallized from ethyl acetate/heptane to give 6.3 g. of the title product, m.p. 145°-147°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[NH2:5].[C:18](=O)([O-])[O-:19].[K+].[K+].C(Cl)(Cl)=O.C1C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([N:5]=[C:18]=[O:19])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: Nc1ccc(OCCc2ccccc2)c(Cl)c1
Reactant: O=C([O-])[O-]
Agent: O=C(Cl)Cl
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: c1ccccc1
Product: O=C=Nc1ccc(OCCc2ccccc2)c(Cl)c1
Temperature: 85 °C

Procedure:
A mixture of 3-chloro-4-(phenethyloxy)aniline (16.06 g; 0.0648 mol), toluene (500 ml) and potassium carbonate (4.5 g; 0.035 mol) is prepared and maintained under nitrogen atmosphere. A. 12.5% solution of phosgene in benzene (65 ml; 0.072 mol) is added to the above mixture. A precipitate forms immediately. The mixture is heated at 85° C. for 45 minutes. By the end of this period the precipitate has dissolved. The reaction mixture is cooled down and filtered. The product is not isolated but rather it is used immediately.
Reaction SMILES: [CH2:1]([N:8]1[CH2:14][CH2:13][C:12](=O)[NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:22]>O1CCOCC1>[CH2:1]([N:8]1[CH2:14][CH2:13][C:12](=[S:22])[NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: O=C1CCN(Cc2ccccc2)CCN1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: S=C1CCN(Cc2ccccc2)CCN1
Temperature: 75 °C
Reaction time: 1 h

Procedure:
To a solution of 1-benzyl-1,4-diazepan-5-one (2.00 g, 9.80 mmol) in anhydrous dioxane (40 mL), sodium bicarbonate (8.81 g, 105 mmol) and phosphorus pentasulfide (2.92 g, 13.1 mmol) were added. The mixture was heated to 75° C. for 6 h. Dioxane was removed under reduced pressure and the residue was treated with water (80 mL). The resultant mixture was stirred at 50° C. for 1 h and then stirred an additional 2 h at 25° C. Sodium chloride (30.0 g) was added to the mixture and the aqueous phase was extracted with dichloromethane. The organic phase was concentrated to yield the desired compound, which was used without further purification.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:7]([N+:10]([O-:12])=[O:11])=[CH:8][CH:9]=1)[CH:5]=O.[C:13]([CH2:15][C:16]([NH2:18])=[O:17])#[N:14].N1CCCCC1>C(O)C>[C:13]([C:15](=[CH:5][C:4]1[CH:3]=[C:2]([F:1])[CH:9]=[CH:8][C:7]=1[N+:10]([O-:12])=[O:11])[C:16]([NH2:18])=[O:17])#[N:14]
Reactant: N#CCC(N)=O
Reactant: O=Cc1cc(F)ccc1[N+](=O)[O-]
Solvent: C1CCNCC1
Solvent: CCO
Product: N#CC(=Cc1cc(F)ccc1[N+](=O)[O-])C(N)=O

Procedure:
A mixture of 3-fluoro-6-nitrobenzaldehyde (10.0 g., 0.0592 mole), 2-cyanoacetamide (5.24 g., 0.0622 mole), piperidine (0.37 g., 4.36 millimole) and ethanol (92 ml.) is heated to reflux on a steam bath for two hours. It is then cooled in an ice-bath whereupon the product precipitates and is recovered by filtration, washed with cold ethanol and dried. Yield = 9.1 g. (65%) of crude product. M.P. 162°-166° C.
Reaction SMILES: C([N:4]1[CH2:9][CH2:8][C:7]2([CH2:14][CH2:13][C:12]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)([N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[CH2:11][CH2:10]2)[CH2:6][CH2:5]1)C=C.CN(C)C1(C2C=CC=CC=2)CCC2(CCNCC2)CC1>>[C:20]1([C:12]2([N:15]3[CH2:16][CH2:17][CH2:18][CH2:19]3)[CH2:11][CH2:10][C:7]3([CH2:6][CH2:5][NH:4][CH2:9][CH2:8]3)[CH2:14][CH2:13]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: C=CCN1CCC2(CC1)CCC(c1ccccc1)(N1CCCC1)CC2
Agent: CN(C)C1(c2ccccc2)CCC2(CCNCC2)CC1
Product: c1ccc(C2(N3CCCC3)CCC3(CCNCC3)CC2)cc1
Yield: 90 %

Procedure:
The reaction was performed starting from 3-allyl-9-phenyl-9-(pyrrolidin-1-yl)-3-azaspiro[5.5]undecane in an analogous manner to stage 9 amine (A1). Yield: 90%