Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[C:13]([C:19]([NH:21][NH2:22])=O)=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=2)(=[O:10])=[O:9])=[CH:4][C:3]=1[C:23]([F:26])([F:25])[F:24].[CH3:27]OC(OC)OC.C(#N)C.[O:37]([C:39]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:40]=1[NH2:41])[CH3:38]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[C:13]([C:19]3[N:41]([C:40]4[CH:42]=[C:43]([F:46])[CH:44]=[CH:45][C:39]=4[O:37][CH3:38])[CH:27]=[N:22][N:21]=3)=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=2)(=[O:9])=[O:10])=[CH:4][C:3]=1[C:23]([F:24])([F:26])[F:25]
Reactant: NNC(=O)c1ncc(Cl)cc1NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Reactant: COC(OC)OC
Reactant: COc1ccc(F)cc1N
Solvent: CC#N
Solvent: CC(=O)O
Product: COc1ccc(F)cc1-n1cnnc1-c1ncc(Cl)cc1NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1

Procedure:
The title compound was prepared according to general Method B using 4-Chloro-N-(5-chloro-2-hydrazinocarbonyl-pyridin-3-yl)-3-trifluoromethyl-benzenesulfonamide (100 mg, 0.234 mmol), trimethylorthoformate (80 mg, 0.60 mmol), acetonitrile (2 mL), 2-methoxyl-5-fluoroaniline (70 mg, 0.50 mmol) and acetic acid (1.0 mL). MS (ES) [M+H]+ expected 562.0. found 562.0.
Reaction SMILES: [CH:1]1(Br)[CH2:4][CH2:3][CH2:2]1.[Mg].II.[NH2:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[C:12]#N.C([O:20]CC)C>>[NH2:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[C:12]([CH:1]1[CH2:4][CH2:3][CH2:2]1)=[O:20]
Reactant: N#Cc1ccccc1N
Reactant: BrC1CCC1
Reactant: CCOCC
Agent: II
Agent: [Mg]
Product: Nc1ccccc1C(=O)C1CCC1
Temperature: 25 °C
Yield: 71 %

Procedure:
Over a period of 1 h a solution of cyclobutyl bromide (13 g, 0.1 mol) in diethyl ether (150 ml) was added dropwise to a slurry of magnesium turnings (2.5 g, 0.11 mol) and a crystal of iodine in diethyl ether (20 ml) at reflux. The mixture was stirred for a further hour whereupon the Grignard solution was cannulated into a pressure equalising dropping funnel, attached to a three-necked round-bottomed flask, which was under an atmosphere of nitrogen. A solution of 2-aminobenzonitrile (3.78 g, 32 mmol) at 0° C. in diethyl ether (50 ml) was treated dropwise with the Grignard reagent prepared above, over a period of 15 min. Once the addition was complete, the mixture was warmed to room temperature and stirred for 16 h under nitrogen. The solution was cooled to 0° C., quenched with 5N hydrochloric acid (20 ml), and basified using solid sodium hydroxide (4 g). The aqueous solution was extracted with ethyl acetate (2×100 ml) and the combined organic layers were dried (Na2SO4) and evaporated. The residue was chromatographed on silica gel using 2:1 petrol:ethyl acetate as the eluant. This gave a yellow oil which was then azeotroped with toluene (2×80 ml) to-give the title compound (4 g, 71%) as a pale yellow solid. mp 55° C. 1H NMR (250 MHz, CDCl3) 5 1.72-2.48 (6H, m), 3.80-4.00 (1H, m), 6.23 (2H, brs), 6.50-6.61 (2H, m), 7.11-7.22 (1H, m), 7.45-7.54 (1H, m).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([F:23])[CH:17]=1.C(O)C.[C:27]1([C:33]([N:35]=[C:36]=[S:37])=[O:34])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1(C)C=CC=CC=1>[C:33]([NH:35][C:36]([NH:20][C:19]1[CH:21]=[CH:22][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[CH:17][C:18]=1[F:23])=[S:37])(=[O:34])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: O=C(N=C=S)c1ccccc1
Reactant: COc1cc2nccc(Oc3ccc(N)c(F)c3)c2cc1OC
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4ccccc4)c(F)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 80 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (76 mg, yield 80%).
Reaction SMILES: NCC[NH:4][C:5](=S)[NH:6][C:7]1[C:15](C)=C2C(C=CN2)=CC=1.[N:18]([C:21]1[C:29]([CH3:30])=[C:28]2[C:24]([CH:25]=[CH:26][NH:27]2)=[CH:23][CH:22]=1)=C=S.C(N)CN>C1(C)C=CC=CC=1>[CH3:30][C:29]1[C:21]([NH:18][N:6]2[CH2:7][CH2:15][N:4]=[CH:5]2)=[CH:22][CH:23]=[C:24]2[C:28]=1[NH:27][CH:26]=[CH:25]2
Reactant: Cc1c(N=C=S)ccc2cc[nH]c12
Reactant: Cc1c(NC(=S)NCCN)ccc2cc[nH]c12
Solvent: NCCN
Solvent: Cc1ccccc1
Product: Cc1c(NN2C=NCC2)ccc2cc[nH]c12

Procedure:
6-[-N′-(2-Aminoethyl)thioureido]-7-methylindole. A solution of 6-isothiocyanato-7-methylindole (0.85 g, 4.52 mmol) in 25 mL of toluene is added to a solution of ethylenediamine (1.06 mL, 15.8 mmol) in 50 mL of toluene. The milky white mixture is stirred for 30 minutes as the desired product precipitates. The reaction is filtered to yield 1.1 g of 6-[-N′-(2-aminoethyl)thioureido]-7-methylindole as a flaky white solid (99% yield).
Reaction SMILES: [N:1]1[C:2]([C:10]2[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=2)[C:13]#[N:14])=[CH:3][N:4]2[C:9]=1[CH:8]=[CH:7][CH:6]=[N:5]2.NO.Cl.CC[N:23](CC)CC.[Cl:28][CH2:29][C:30](Cl)=[O:31]>CCO.C1(C)C=CC=CC=1>[Cl:28][CH2:29][C:30]1[O:31][N:23]=[C:13]([C:12]2[CH:11]=[C:10]([C:2]3[N:1]=[C:9]4[CH:8]=[CH:7][CH:6]=[N:5][N:4]4[CH:3]=3)[CH:17]=[CH:16][CH:15]=2)[N:14]=1
Reactant: O=C(Cl)CCl
Reactant: CCN(CC)CC
Reactant: N#Cc1cccc(-c2cn3ncccc3n2)c1
Agent: Cl
Agent: NO
Solvent: Cc1ccccc1
Solvent: CCO
Product: ClCc1nc(-c2cccc(-c3cn4ncccc4n3)c2)no1

Procedure:
A mixture of 0.5 mmol 3-(imidazo[1,2-b]pyridazin-2-yl)benzonitrile, 1 mmol NH2OH.HCl and 1 mmol Et3N in EtOH was stirred at reflux for 4 h then cooled. Excess of solvent was removed in vacuo to afford the crude product. 2-chloroacetyl chloride (2 mmol) was added to the mixture solution of the crude product in Toluene (15 ml) at room temperature and then the mixture was heated to reflux for 5 h. The mixture was concentrated in vacuo and the crude product was purified by column chromatography on silica gel to give the 2-(3-(5-(chloromethyl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-b]pyridazine.
Reaction SMILES: [CH:1]([N:4]([CH:16]([CH3:18])[CH3:17])[CH2:5][CH2:6][CH:7]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:8]#[N:9])([CH3:3])[CH3:2].[NH2-].[Na+].C1(C)C=CC=CC=1.Cl[CH2:29][CH2:30][N:31]([CH:35]([CH3:37])[CH3:36])[CH:32]([CH3:34])[CH3:33]>O>[CH:16]([N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6][C:7]([CH2:29][CH2:30][N:31]([CH:35]([CH3:37])[CH3:36])[CH:32]([CH3:34])[CH3:33])([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:8]#[N:9])([CH3:18])[CH3:17]
Reactant: CC(C)N(CCC(C#N)c1ccccc1)C(C)C
Reactant: CC(C)N(CCCl)C(C)C
Agent: [NH2-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)N(CCC(C#N)(CCN(C(C)C)C(C)C)c1ccccc1)C(C)C

Procedure:
A solution of 20 parts of α-[2-(diisopropylamino)ethyl]-α-phenylacetonitrile and 4 parts of sodium amide in 180 parts by volume of toluene is heated to about 100° C. over a period of 15 minutes and then 18 parts of 2-chloro-N,N-diisopropylethylamine in 70 parts by volume of toluene is added slowly over a period of 20 minutes. This mixture is heated at 105°-110° C. for an hour and then cooled to room temperature when 200 parts by volume of water is added. The organic layer is separated, dried over calcium sulfate, concentrated and distilled to afford α,α-bis[2-(diisopropylamino)ethyl]-α-phenylacetonitrile as an oil. This compound is identical with the compound of Example 2, Method A.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][N:5]([CH3:16])[C:6]=1[C:7]1[CH:8]=[C:9]([C:13]([OH:15])=O)[S:10][C:11]=1[CH3:12].[NH2:17][C@@H:18]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=1)[CH2:19][N:20]1[C:28](=[O:29])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]1=[O:30].CC(OC(N[C@H](C(O)=O)CC1C=CC=CC=1C(F)(F)F)=O)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH3:16])[C:6]=1[C:7]1[CH:8]=[C:9]([C:13]([NH:17][C@@H:18]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:39])[F:40])[CH:33]=2)[CH2:19][N:20]2[C:21](=[O:30])[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:28]2=[O:29])=[O:15])[S:10][C:11]=1[CH3:12]
Reactant: Cc1sc(C(=O)O)cc1-c1c(Br)cnn1C
Reactant: N[C@@H](Cc1cccc(C(F)(F)F)c1)CN1C(=O)c2ccccc2C1=O
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1C(F)(F)F)C(=O)O
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClC(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1sc(C(=O)N[C@@H](Cc2cccc(C(F)(F)F)c2)CN2C(=O)c3ccccc3C2=O)cc1-c1c(Br)cnn1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.7 %

Procedure:
To a 50 mL round-bottomed flask was added 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylic acid (180 mg, 0.60 mmol) [prepared according to the procedure of Example 159], 2-{(2S)-2-amino-3-[3-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (203 mg, 0.58 mmol) [prepared according to the procedure of Preparation 6 except substituting N-{[(1,1-dimethylethyl)oxy]carbonyl}-3-(trifluoromethyl)-L-phenylalanine (4.98 g, 15.0 mmol) for N-{[(1,1-dimethylethyl)oxy]carbonyl}-2-(trifluoromethyl)-L-phenylalanine] and PyBrop (340 mg, 0.72 mmol) in Chloroform (6 mL). DIEA (530 μL, 3.03 mmol) was added and the reaction stirred overnight at room temperature. The mixture was adsorbed onto silica and purified via column chromatography (25-70% EtOAc/Hex) affording the title compound (259 mg, 0.41 mmol, 69%): LC-MS (ES) m/z=633 (M+H)+.
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:9]1[C@@:13]2([CH3:29])[CH2:14][CH2:15][C@@H:16]3[C@@:21]4([CH3:27])[CH2:22][CH2:23][C@@H:24]([OH:26])[CH2:25][C@H:20]4[CH2:19][C@@H:18]([OH:28])[C@H:17]3[C@@H:12]2[CH2:11][CH2:10]1)[CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6].N1C=CC=CC=1.CN(C1C=CC=CN=1)C.CS(Cl)(=O)=[O:47]>ClCCl>[CH3:1][C@@H:2]([C@@H:9]1[C@@:13]2([CH3:29])[C@@H:14]([OH:47])[CH2:15][C@@H:16]3[C@@:21]4([CH3:27])[CH2:22][CH2:23][C@@H:24]([OH:26])[CH2:25][C@H:20]4[CH2:19][C@@H:18]([OH:28])[C@H:17]3[C@@H:12]2[CH2:11][CH2:10]1)[CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3C[C@H](O)[C@]12C
Temperature: 0 °C

Procedure:
Methyl chenodeoxycholate (27 g, 61.5 mmol) is dissolved in 100 mL dichloromethane (DCM), pyridine (20 mL). Dimethylaminopyridine (DMAP) (1.22 g, 10 mmol) is then added. The reaction mixture is chilled to 0° C., and methanesul-fonyl chloride (7.5 mL, 11.0 g, 96.7 mmol) is added dropwise. The reaction mixture is heated at 60° C. for 3 h, cooled to r.t., washed with 5% HCl, water, sodium bicarbonate, brine, and dried over sodium sulfate. The solvent is evaporated under reduced pressure (1 mm Hg, 80° C. in a bath) to give mesylate 1 as a thick oil, weight 27 g (90%). This material is used in the next step without further purification.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6](=[O:9])[N:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4]=1[S-:16])#[N:2].[Na+].Cl[CH2:19][C:20]#[N:21].O>CC#N>[NH2:2][C:1]1[C:3]2[CH:8]=[CH:7][C:6](=[O:9])[N:5]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:4]=2[S:16][C:19]=1[C:20]#[N:21]
Reactant: N#Cc1ccc(=O)n(-c2ccccc2)c1[S-]
Reactant: N#CCCl
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: N#Cc1sc2c(ccc(=O)n2-c2ccccc2)c1N

Procedure:
A mixture of Example 1 (100 g at 100%) and chloracetonitrile (30.4 mL) in MeCN (500 mL) was heated at reflux for 2 h. The mixture was cooled, initially to 40° C. when water (300 mL) was added, and then to +10° C. The reaction was maintained at +10° C. for at least 1 h when the product was recovered by filtration. The filter cake was washed with cold (+10° C.) H2O (500 mL) followed by a cold (+10° C.) mixture of MeCN and H2O (1:1, 300 mL). The product was dried under vacuum at 50° C. to constant weight to give the title compound as an off-white solid (100.9 g). δH (DMSO-d6) 7.90 (1H, d, J 9.6 Hz), 7.46-7.33 (3H, m), 7.25 (2H, m), 6.95 (2H, br s), 6.35 (1H, d, J 9.6 Hz). LCMS (ES+) RT 2.69 minutes, 268 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[Cl:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([Cl:32])[C:28]=1[CH2:29]CBr.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:21])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:29][C:28]2[C:27]([Cl:32])=[CH:26][N:25]=[CH:24][C:23]=2[Cl:22])=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:7]
Reactant: Clc1cncc(Cl)c1CCBr
Reactant: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COC(=O)[C@H](Cc1ccc(OCc2c(Cl)cncc2Cl)cc1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.4 %

Procedure:
A mixture of N-Boc-L-tyrosine methyl ester (11.95 g, 40.57 mmol), 3,5-dichloro-4-bromethyl pyridine (see International Patent Application No. PCT/GB99/00589; 10.74 g, 44.56 mmol) and caesium carbonate (14.52 g, 44.56 mmol) in DMF (100 ml) was stirred at room temperature overnight. The solvent was removed in vacuo and the residue partitioned between ethyl acetate and aqueous NaHCO3. The organic layer was washed with citric acid (10%×2), aqueous NaHCO3 (×2) and brine, dried (MgSO4) and concentrated in vacuo to give the title compound as a brown solid (18.0 g, 98%). δH (d6 DMSO) 8.72 (2H, s), 7.25 (1H, d, J 8.2 Hz), 7.19 (2H, d, 18.5 Hz), 6.97 (2H, d, 18.5 Hz), 5.20 (2H, s), 4.13 (1H, m), 3.61 (3H, s), 2.95 (1H, dd, J 13.7, 5.0 Hz), 2.82 (1H, m), 1.32 (9H, s) m/z (ESI, 60V) 477 (M++H).
Reaction SMILES: [Br:1][C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH:12]1[CH2:17]CCCO1.[O:22]1[CH:27]=[CH:26][CH2:25][CH2:24][CH2:23]1.C1(C)C=CC(S(O)(=O)=[O:35])=CC=1>C1COCC1>[Br:1][C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:17][O:35][CH:27]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: C1=COCCC1
Reactant: Brc1ccccc1COCCOCCOC1CCCCO1
Solvent: C1CCOC1
Product: Brc1ccccc1COCCOCCOCCOC1CCCCO1

Procedure:
The compound was prepared and worked up as described in the preparation of compound 420. Starting compounds were compound 416 (2.82 g, 8.9 mmol) in 6 mL dry THF, 3,4-dihydro-2H-pyran (0.89 mL, 9.8 mmol) and p-toluenesulfonic acid (37 mg, 0.19 mmol). The crude product was purified by flash chromatography using EtOAc/petroleum ether 1:3 as the eluent to afford the title compound as a pale yellow oil.
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[C:6]([OH:10])(=[O:9])[CH:7]=[CH2:8].[C:11]([OH:15])(=[O:14])[CH:12]=[CH2:13].[CH2:16]([C:18]([CH2:23]O)([CH2:21]O)[CH2:19][CH3:20])O.C1CC=CC=1>>[CH3:20][CH2:19][C:18]([CH2:23][O:14][C:11]([CH:12]=[CH2:13])=[O:15])([CH2:21][O:9][C:6]([CH:7]=[CH2:8])=[O:10])[CH2:16][O:4][C:1]([CH:2]=[CH2:3])=[O:5]
Reactant: C=CC(=O)O
Reactant: CCC(CO)(CO)CO
Agent: C1=CCC=C1
Product: C=CC(=O)OCC(CC)(COC(=O)C=C)COC(=O)C=C

Procedure:
Trimethylolpropane triacrylate (177.8 g, 0.60 mole) and cyclopentadiene (112.0 g, 1.8 mole) were stirred at 25-40° C. for 21 hours to obtain Diels-Alder adduct of TMPTA-CPD. The obtained TMPTA-CPD (165.0 g, 0.33 mole), fumaric acid (38.3 g, 0.33 mole) and THQ (0.07 g) were heated to 190° C. in 3 hours under nitrogen and held for 12 hours to obtain a tricarboxylic acid with an acid number of 55 mg KOH/g, glycidyl methacrylate (28.4 g, 0.20 mole) and triethyl benzyl ammonium chloride (0.15 g) were heated to 110-120° C. and held for 2 hours to obtain an acrylic ester with an acid number of 22. The resulting acrylic ester was dissolved in styrene with 0.04 g of THQ to obtain a resin with 30% styrene. The resin solution has a viscosity of 430 cps, gel time 9.0 min, cure time 12.0 min, and peak exotherm 210° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:14]2[O:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[NH:6][C:5]=2[CH:4]=1.[CH3:17][CH:18]1[NH:22][C:21](=O)[CH2:20][CH2:19]1.P(Cl)(Cl)(Cl)=O>>[CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:14]2[O:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[N:6]([C:21]3[CH2:20][CH2:19][CH:18]([CH3:17])[N:22]=3)[C:5]=2[CH:4]=1
Reactant: CC1CCC(=O)N1
Reactant: COc1ccc2c(c1)Nc1ccccc1O2
Solvent: O=P(Cl)(Cl)Cl
Product: COc1ccc2c(c1)N(C1=NC(C)CC1)c1ccccc1O2

Procedure:
Reaction of 2-methoxyphenoxazine, 5-methyl-2-pyrrolidinone and phosphorus oxychloride according to the procedure of Example 1 provides the free base 2-METHOXY-10-(5-METHYL-1-PYRROLIN-2YL)PHENOXAZINE as an oil. Conversion of the free base to the hydrochloride salt affords 2METHOXY-10-(5-METHYL-1-PYRROLIN-2-YL)-PHENOXAZINE HYDROCHLORIDE, m.p. 223.5°-224.5°C. (dec.)(corr.), as the hemihydrate by trituration with acetone.
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:11]=[CH:10][O:9][C:8]=1[C:12]1([CH3:17])[O:16]CCO1.[C:18](=[O:20])=[O:19].C(=O)([O-])[O-].[Na+].[Na+]>CCCCCC.C(OCC)C.O>[C:12]([C:8]1[O:9][CH:10]=[CH:11][C:7]=1[C:18]([OH:20])=[O:19])(=[O:16])[CH3:17]
Reactant: CC1(c2occc2Br)OCCO1
Reactant: O=C=O
Agent: O=C([O-])[O-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Solvent: CCCCCC
Product: CC(=O)c1occc1C(=O)O
Reaction time: 0.5 h

Procedure:
At 0°, a solution of anhydrous ferric chloride (2.7 g, 17.0 mmol) in 50 ml of nitromethane is added portionwise with stirring over a period of 5 hours to a mixture of 3-bromofuran (25.0 g, 170.0 mmol) and acetic anhydride (20.4 g, 200.0 mmol) in 50 ml of nitromethane. After addition is completed, the resulting mixture is stirred at RT for 17 hours and is then evaporated in vacuo. The residue is taken up in 200 ml of diethyl ether, treated with 3.0 g of activated charcoal and filtered. The filtrate is washed with 5% sodium bicarbonate and dried and the solvent is removed by rotoevaporation to give, after purification, 2-acetyl-3-bromofuran. A well-stirred mixture of 2-acetyl-3-bromofuran (13.7 g, 72.0 mmol), ethylene glycol (5.9 g, 94.0 mmol), p-toluenesulfonic acid (p-TSOH; 20 mg) and benzene (50 ml) is refluxed for 9 hours, after which additional ethylene glycol (1.8 g, 29.0 mmol) and p-TSOH (5 mg) is added and the refluxing is continued a further 16 hours. The reaction mixture is then washed with sat. sodium bicarbonate and with water and is dried. The solvent is removed by rotoevaporation to give 2-(3-bromo-2-furyl)-2-methyl-1,3-dioxolane. To a solution of 1.6M butyllithium in hexane (38 ml) and dry diethylether (40 ml), under N2, is added dropwise with stirring a solution of the above dioxolane (11.18 g, 48.0 mmol) in 40 ml of ether, keeping the temperature below -68°. After addition is completed, the mixture is stirred for 30 min. at -70°, and then a slurry of CO2 (50.0 g) in 100 ml of dry diethyl ether is added. The mixture is kept at -65° for 15 min. and is then allowed to warm to 10°. Water is added, followed by 10% sodium carbonate. The phases are separated and the organic phase is extracted. The combined aqueous phases are acidified with conc. HCl and extracted with ether. The organic phases are combined and dried and the solvent is removed by rotoevaporation. The resulting product is suspended in 5% HCl (85 ml) and stirred at RT for 2 hours, then extracted with ether and the combined ether phases are dried and evaporated to dryness. The crude product is purified to give 2-acetyl-3-furancarboxylic acid.
Reaction SMILES: [Br:1][C:2]([CH3:7])([CH3:6])[C:3](Cl)=[O:4].[NH2:8][C:9]1[C:10]([OH:26])=[C:11]([C:23](=[O:25])[CH3:24])[CH:12]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=1.C(OCC)(=O)C.Cl>N1C=CC=CC=1>[C:23]([C:11]1[C:10]([OH:26])=[C:9]([NH:8][C:3](=[O:4])[C:2]([Br:1])([CH3:7])[CH3:6])[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:12]=1)(=[O:25])[CH3:24]
Reactant: CC(C)(Br)C(=O)Cl
Reactant: CC(=O)c1cc(OCc2ccccc2)cc(N)c1O
Agent: Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CC(=O)c1cc(OCc2ccccc2)cc(NC(=O)C(C)(C)Br)c1O
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
4.64 g (25 mmol) 2-bromo-2-methyl-propionyl chloride are added dropwise at 5-20° C. to a solution of 5.15 g (20 mmol) 1-(3-amino-5-benzyloxy-2-hydroxy-phenyl)-ethanone in 20 mL pyridine. After the addition has ended the mixture is stirred for 15 minutes, combined with ice water and 100 mL ethyl acetate and acidified with conc. hydrochloric acid. The organic phase is separated off, washed with water and dried with sodium sulphate. After the solvent has been distilled off the residue is crystallised from a diethyl ether/petroleum ether mixture.
Reaction SMILES: [C:1]1([C:7]2[CH:23]=[CH:22][C:10]([O:11][C:12]3[CH:13]=[C:14](C#N)[C:15](=[CH:18][CH:19]=3)C#N)=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)[OH:25].[C:29]([OH:32])(=[O:31])[CH3:30]>>[C:1]1([C:7]2[CH:23]=[CH:22][C:10]([O:11][C:12]3[CH:13]=[C:14]4[C:15](=[O:25])[O:32][C:29](=[O:31])[C:30]4=[CH:18][CH:19]=3)=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)O
Reactant: N#Cc1ccc(Oc2ccc(-c3ccccc3)cc2)cc1C#N
Reactant: O=S(=O)(O)O
Product: O=C1OC(=O)c2cc(Oc3ccc(-c4ccccc4)cc3)ccc21
Temperature: 120 °C
Yield: 99 %

Procedure:
A 1 L 3-necked round-bottomed flask was equipped with a condenser, mechanical stirrer, and an addition funnel. The flask was charged with 4-(4-phenylphenoxy)-phthalonitrile (71 g, 0.24 mole) and acetic acid (450 mL). The addition funnel was filled with 70% sulfuric acid (200 mL). The solution was heated to 120° C., and then sulfuric was added drop-wise into the reaction mixture over 2 hours. The resulting mixture was refluxed overnight (12 hours). The reaction mixture was cooled to room temperature, and poured into an ice-water mixture (˜1 kg). The product precipitated out as a pale brown powder. The powder was collected by filtration, and it was further purified by recrystallization using acetic anhydride (255 mL). The crystal was collected by filtration and dried in a vacuum oven at 150° C. overnight to give the desired product (75.0 g, 99% yield). MP 199° C. 1H NMR (δ, D6-DMSO): 8.11 (d, 1H), 7.82 (d, 2H), 7.71 (d, 2H), 7.58 (dd, 1H), 7.55-7.35 (m, 4H), 7.30 (d, 2H).
Reaction SMILES: [NH2:1][C@H:2]([C:10]([NH:12][C@H:13]([C:15]([NH:17][C@H:18]([C:23]([NH:25][CH2:26][C:27]([O:29][CH3:30])=[O:28])=[O:24])[C@H:19]([CH2:21][CH3:22])[CH3:20])=[O:16])[CH3:14])=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].[CH:31]1[CH:36]=[CH:35][C:34]([CH2:37][O:38][C:39]([NH:41][C@H:42]([C:48](OC2C=CC([N+]([O-])=O)=CC=2)=[O:49])[CH2:43][CH2:44][C:45]([NH2:47])=[O:46])=[O:40])=[CH:33][CH:32]=1>CN(C)C=O.CCOCC>[NH:41]([C:39]([O:38][CH2:37][C:34]1[CH:35]=[CH:36][CH:31]=[CH:32][CH:33]=1)=[O:40])[C@H:42]([C:48]([NH:1][C@H:2]([C:10]([NH:12][C@H:13]([C:15]([NH:17][C@H:18]([C:23]([NH:25][CH2:26][C:27]([O:29][CH3:30])=[O:28])=[O:24])[C@H:19]([CH2:21][CH3:22])[CH3:20])=[O:16])[CH3:14])=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:6])([CH3:8])[CH3:7])=[O:49])[CH2:43][CH2:44][C:45](=[O:46])[NH2:47]
Reactant: CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)OC(C)(C)C)C(=O)NCC(=O)OC
Reactant: NC(=O)CC[C@H](NC(=O)OCc1ccccc1)C(=O)Oc1ccc([N+](=O)[O-])cc1
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)OCc1ccccc1)[C@@H](C)OC(C)(C)C)C(=O)NCC(=O)OC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4.6 g of the H-Thr(tBu)-Ala-Ile-Gly-OMe described under 28) in 30 ml of dimethylformamide, are mixed with 3.5 g of Z-Gln-ONP and stirred at room temperature until the mixture becomes solid. After allowing to stand overnight the mixture is diluted with ether and the precipitate is filtered off and washed with ether until free of nitrophenol. The protected pentapeptide shows Rf = 0.14 in the system chloroform-methanol (95:5) in a thin layer chromatogram on silica gel. Melting point: > 250° C.