Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:4][CH2:5][CH2:6][O:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[C:10]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)=[C:21]([Cl:33])[CH:20]=1)=[N:11][CH:12]=[N:13]2)[CH:2]=[CH2:3].[C:34](Cl)(=[O:36])[CH3:35]>>[CH2:1]([N:4]([CH2:5][CH2:6][O:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[C:10]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)=[C:21]([Cl:33])[CH:20]=1)=[N:11][CH:12]=[N:13]2)[C:34](=[O:36])[CH3:35])[CH:2]=[CH2:3]
Reactant: C=CCNCCOc1cccc2ncnc(Nc3ccc(OCc4ccccn4)c(Cl)c3)c12
Reactant: CC(=O)Cl
Product: C=CCN(CCOc1cccc2ncnc(Nc3ccc(OCc4ccccn4)c(Cl)c3)c12)C(C)=O
Yield: 47 %

Procedure:
The procedure described in Example 5 was repeated using 5-[2-(allylamino)ethoxy]-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]quinazolin-4-amine and acetyl chloride to give the title compound in 47% yield; NMR spectrum (DMSO-d6) 1.95 (s, 3H), 3.86 (t, 2H), 4.02-4.06 (m, 2H), 4.38 (t, 2H), 5.07-5.18 (m, 2H), 5.31 (s, 2H), 5.82-5.92 (m, 1H), 7.14 (d, 1H), 7.25 (d, 1H), 7.32-7.40 (m, 2H), 7.55-7.61 (m, 2H), 7.70-7.75 (m, 1H), 7.86-7.93 (m, 2H), 8.44 (s, 1H), 8.61 (d, 1H), 9.76 (s, 1H); Mass spectrum MH+ 504.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22](OC4C=CC=CC=4)=[O:23])=[CH:17][N:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.O.[NH2:32][NH2:33]>O1CCOCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:23])[NH:32][NH2:33])=[CH:17][N:16]=3)[CH2:13][CH2:14]2)=[CH:5][CH:4]=1
Reactant: NN
Reactant: COc1ccc(N2CCN(c3ccc(NC(=O)Oc4ccccc4)cn3)CC2)cc1
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(N2CCN(c3ccc(NC(=O)NN)cn3)CC2)cc1

Procedure:
A mixture of the product of part (iii) (2.8 g, 6.9 mmole) and hydrazine hydrate (7.5 ml, 150 mmole) in 1,4-dioxane (50 ml) was heated under reflux for 1.5 hours. The cooled mixture was filtered to provide a solid which was washed with ether to yield the desired product, m.p. 280°-282° (2.0 g, 85%), which was used without further purification.
Reaction SMILES: C([O:5][C:6](=[O:22])[CH2:7][N:8]([C:13](=[O:21])[CH:14]([CH3:20])[CH2:15][S:16][C:17](=[O:19])[CH3:18])[CH:9]1[CH2:12][CH2:11][CH2:10]1)(C)(C)C.C[Si](I)(C)C>C(Cl)Cl>[C:17]([S:16][CH2:15][CH:14]([CH3:20])[C:13]([N:8]([CH:9]1[CH2:10][CH2:11][CH2:12]1)[CH2:7][C:6]([OH:22])=[O:5])=[O:21])(=[O:19])[CH3:18]
Reactant: CC(=O)SCC(C)C(=O)N(CC(=O)OC(C)(C)C)C1CCC1
Agent: C[Si](C)(C)I
Solvent: ClCCl
Product: CC(=O)SCC(C)C(=O)N(CC(=O)O)C1CCC1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 93.2 %

Procedure:
To a stirred, argon flushed solution of N-(3-acetylthio-2-methyl-propanoyl)-N-cyclobutylglycine t-butyl ester (28.4 g, 0.086 mol) in methylene chloride was added trimethylsilyl iodide (18.0 g, 0.09 mol). After stirring at room temperature for 40 minutes the reaction was quenched by the addition of 50 ml of water. To this mixture, after stirring for 1 hour, was added 150 ml of 4% aqueous HCl, and the mixture was extracted with methylene chloride. The organic extracts were combined, dried over MgSO4, and evaporated to yield 21.9 g (90%) of the desired product as a light brown oil. This compound was characterized as its DCHA salt, prepared by adding DCHA to an ethereal solution of the compound until bringing the solution to pH 9. The salt was collected and recrystallized in acetonitrile to yield a white crystalline solid, m.p. 162.5°-164.5° C.
Reaction SMILES: [ClH:1].[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[CH:21]=[C:20](Br)[CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2.[O:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=2)[CH2:25][CH2:24]1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[ClH:1].[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[CH:21]=[C:20]([C:32]4[CH:31]=[CH:30][C:29]([N:26]5[CH2:25][CH2:24][O:23][CH2:28][CH2:27]5)=[CH:34][CH:33]=4)[CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2
Reactant: OB(O)c1ccc(N2CCOCC2)cc1
Reactant: O=C(N[C@H]1CN2CCC1CC2)c1cc2ccc(Br)cc2s1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: Cl
Solvent: CN(C)C=O
Product: O=C(N[C@H]1CN2CCC1CC2)c1cc2ccc(-c3ccc(N4CCOCC4)cc3)cc2s1
Temperature: 80 °C
Reaction time: 16 h

Procedure:
100 mg (0.25 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 11A) and 51.5 mg (0.25 mmol) of 4-morpholinophenylboronic acid are introduced into 1 ml of DMF. Addition of 0.37 ml of 2 M sodium carbonate solution and 10.2 mg (0.01 mmol) of PdCl2(dppf) is followed by heating to 80° C. After 16 h, a further 51.5 mg (0.25 mmol) of 4-morpholinophenylboronic acid, 0.37 ml of 2 M sodium carbonate solution and 10.2 mg (0.01 mmol) of PdCl2(dppf) are added. The mixture is heated at 80° C. for a further 4 h. After cooling, the reaction mixture is filtered through kieselguhr and purified by preparative HPLC. The product fractions are concentrated and, after addition of a 5:1 mixture of methanol and 4 M hydrogen chloride in dioxane, again concentrated. Drying under high vacuum results in 83 mg (69% of theory) of the title compound.
Reaction SMILES: [OH:1][C:2]([CH3:16])([CH3:15])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][CH:6]=1)=O.N1C=CC=CC=1.C([O:26][CH2:27][C:28](Cl)=[O:29])(=O)C.C1CCN2C(=NCCC2)CC1>CC#N.CCOC(C)=O.O.[Cl-].[Na+].O>[CH3:15][C:2]1([CH3:16])[O:1][C:27](=[O:26])[C:28]([OH:29])=[C:3]1[C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][CH:6]=1
Reactant: CC(C)(O)C(=O)c1ccc(S(C)(=O)=O)cc1
Reactant: CC(=O)OCC(=O)Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: C1CCC2=NCCCN2CC1
Solvent: c1ccncc1
Product: CC1(C)OC(=O)C(O)=C1c1ccc(S(C)(=O)=O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 42.9 %

Procedure:
To a 0° C. solution of the alcohol of Example 1, Step 3 (14.0 g, 57.8 mmol) in CH3CN (180 mL) were added pyridine (10.0 mL) and acetoxyacetyl chloride (12.7 g, 93.0 mmol) after a period of 7 h at r.t., DBU (15.0 ml) was added to the reaction mixture. After a period of 1 h at 80° C., a second portion of DBU (20.0 mL) was added. The reaction mixture was kept at 80° C. for 18 h. The reaction mixture allowed to cool to r.t. The mixture was diluted with EtOAc (500 mL) and H2O (500 mL) and acidified with 6NHCl. After the addition of brine (100 mL), the aqueous phase was extracted 2 times with EtOAc. The organic phase was evaporated to provide a brown residue. To the solid was added a 2:1 mixture of CH2Cl2- toluene (150 mL). The solid was filtered and washed with CH2Cl2- toluene to provide 7.0 g of the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]2[N:8]=[CH:9][NH:10][C:6]=2[CH:5]=1)([O-:3])=[O:2].[CH2:13]([Mg]Br)[CH2:14][CH3:15].ClC1C(=O)C(Cl)=C(Cl)C(=O)C=1Cl>C1COCC1>[CH2:13]([C:5]1[C:6]2[NH:10][CH:9]=[N:8][C:7]=2[CH:11]=[CH:12][C:4]=1[N+:1]([O-:3])=[O:2])[CH2:14][CH3:15]
Reactant: O=[N+]([O-])c1ccc2nc[nH]c2c1
Reactant: CCC[Mg]Br
Agent: O=C1C(Cl)=C(Cl)C(=O)C(Cl)=C1Cl
Solvent: C1CCOC1
Product: CCCc1c([N+](=O)[O-])ccc2nc[nH]c12
Temperature: -15 °C
Reaction time: 2 h
Yield: 51.4 %

Procedure:
To a solution of 5-nitrobenzimidazole (2.3 g, 14 mmol) was added 14 ml of n-PrMgBr solution (42 mmol) and reaction mixture was stirred for 2 h at −15° C. The reaction was quenched by adding a solution of tetrachloro-1,4-benzoquinone (4 g, 16 mmol) in 10 ml of THF. The reaction mixture was concentrated in vacuo to provide an oil, which was subjected to column chromatographic separation (EtOAc, neat) to provide 1.4 g (7.2 mmol, 52%) of 4-n-propyl-5-nitrobenzimidazole, which was converted to the corresponding amine (1.2 g, >95%) by hydrogenation(H2, Pd/C).
Reaction SMILES: [Si]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16](=O)[CH:17]([O:21]CC)OCC)=[CH:11][CH:10]=1)(C(C)(C)C)(C)C.[NH2:25][C:26]1[C:35]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[N:34][C:33]2[C:32]3[CH:43]=[CH:44][C:45]([OH:47])=[CH:46][C:31]=3[CH:30]=[CH:29][C:28]=2[N:27]=1.Cl>C(O)C.O>[CH:40]1[CH:39]=[CH:38][C:37]([CH2:36][C:35]2[NH:34][C:33]3[C:32]4[CH:43]=[CH:44][C:45]([OH:47])=[CH:46][C:31]=4[CH:30]=[CH:29][C:28]=3[N:27]3[C:26]=2[N:25]=[C:16]([CH2:15][C:12]2[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=2)[C:17]3=[O:21])=[CH:42][CH:41]=1
Reactant: CCOC(OCC)C(=O)Cc1ccc(O[Si](C)(C)C(C)(C)C)cc1
Reactant: Nc1nc2ccc3cc(O)ccc3c2nc1Cc1ccccc1
Agent: Cl
Solvent: O
Solvent: CCO
Product: O=c1c(Cc2ccc(O)cc2)nc2c(Cc3ccccc3)[nH]c3c4ccc(O)cc4ccc3n1-2
Temperature: 0 °C
Reaction time: 18 h
Yield: 13260870 %

Procedure:
Under an argon atmosphere, to a solution of 3-(4-(tert-butyldimethylsilyloxy)phenyl)-1,1-diethoxypropan-2-one (15) (101 mg, 286 μmol) in ethanol (2 mL) and water (0.4 mL) was added 3-amino-2-benzylbenzo[f]quinoxalin-8-ol (14) (55.5 mg, 184 μmol). After cooling to 0° C., to the mixture was further added conc. hydrochloric acid (0.20 mL). The mixture was heated to 80° C. and stirred overnight (18 hours). After cooling to room temperature and concentration under reduced pressure, the residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=1/1→1/2→ethyl acetate alone) in an argon flow to give v-coelenterazine (2, v-CTZ) (10.9 mg, 24.4 mol, 13.2%) as ocherous powders. TLC Rf=0.50 (n-hexane/ethyl acetate=1/1); 1H NMR (500 MHz, CD3OD) δ 4.08 (s, 2H), 4.51 (s, 2H), 6.69-6.72 (AA′BB′, 2H), 7.17-7.24 (m, 5H), 7.29 (t, 2H, J=7.5 Hz), 7.43 (d, 2H, J=7.5 Hz), 7.63 (d, 1H, J=8.5 Hz), 8.40 (br, 1H), 9.26 (br, 1H).
Reaction SMILES: CC([N:5]([C@@H:9]([C:12]([NH:14][C:15]1[CH:16]=[N:17][C:18]([O:21][C:22]2[C:27]3[C:28]4([CH2:31][O:32][C:26]=3[CH:25]=[CH:24][CH:23]=2)[CH2:30][CH2:29]4)=[CH:19][CH:20]=1)=[O:13])[CH2:10][CH3:11])C(=O)[O-])(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>ClCCl>[NH2:5][C@H:9]([CH2:10][CH3:11])[C:12]([NH:14][C:15]1[CH:16]=[N:17][C:18]([O:21][C:22]2[C:27]3[C:28]4([CH2:31][O:32][C:26]=3[CH:25]=[CH:24][CH:23]=2)[CH2:30][CH2:29]4)=[CH:19][CH:20]=1)=[O:13]
Reactant: CC[C@H](C(=O)Nc1ccc(Oc2cccc3c2C2(CC2)CO3)nc1)N(C(=O)[O-])C(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC[C@@H](N)C(=O)Nc1ccc(Oc2cccc3c2C2(CC2)CO3)nc1
Reaction time: 2 h
Yield: 92.9 %

Procedure:
To a solution of 1,1-dimethylethyl[(1R)-1-({[6-(spiro[1-benzofuran-3,1′-cyclopropan]-4-yloxy)-3-pyridinyl]amino}carbonyl)propyl]carbamate (Intermediate 88, 128 mg) in dry dichloromethane (3 ml) at 0° C. TFA (0.9 mL, 11.68 mmol) was slowly added and the reaction mixture was stirred for 2 hours at the same temperature. The reaction was diluted with dichloromethane (10 ml) and an aqueous saturated solution of NaHCO3 was added while the pH was allowed to reach ˜8. Two phases were separated and the aqueous layer was re-extracted with dichloromethane (10 ml). The organic layers were combined, dried over sodium sulphate, filtered and evaporated affording the title compound as a colourless oil (92 mg).
Reaction SMILES: Br[C:2]1[CH:35]=[CH:34][C:5]([CH2:6][C:7]2[N:8]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[S:30](=[O:32])(=[O:31])[NH:29][C:28](=[O:33])[CH2:27]4)=[CH:22][CH:21]=3)[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[N:11]=2)=[CH:4][CH:3]=1.[CH:36]1([C:41]2[CH:46]=[CH:45][C:44](B(O)O)=[CH:43][CH:42]=2)[CH2:40][CH2:39][CH2:38][CH2:37]1>>[CH:36]1([C:41]2[CH:42]=[CH:43][C:44]([C:2]3[CH:3]=[CH:4][C:5]([CH2:6][C:7]4[N:8]([C:20]5[CH:21]=[CH:22][C:23]([N:26]6[S:30](=[O:31])(=[O:32])[NH:29][C:28](=[O:33])[CH2:27]6)=[CH:24][CH:25]=5)[CH:9]=[C:10]([C:12]5[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=5[Cl:19])[N:11]=4)=[CH:34][CH:35]=3)=[CH:45][CH:46]=2)[CH2:37][CH2:38][CH2:39][CH2:40]1
Reactant: O=C1CN(c2ccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(Br)cc3)cc2)S(=O)(=O)N1
Reactant: OB(O)c1ccc(C2CCCC2)cc1
Product: O=C1CN(c2ccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(-c4ccc(C5CCCC5)cc4)cc3)cc2)S(=O)(=O)N1

Procedure:
5-{4-[2-(4-Bromo-benzyl)-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,2,5-thiadiazolidine-3-one-1,1-dioxide (59 mg, 0.1 mmol) was treated as described in general procedure G using 4-cyclopentylphenylboronic acid (38 mg, 0.2 mmol) to give 5-{4-[2-(4′-cyclopentyl-biphenyl-4-ylmethyl)-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,2,5-thiadiazolidine-3-one-1,1-dioxide.
Reaction SMILES: [F:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:36])[CH:9]=2)=[CH:4][CH:3]=1.[ClH:39]>ClCCl>[ClH:39].[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[CH2:28][NH:27][CH2:26][CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:36])[CH:9]=2)=[CH:37][CH:38]=1
Reactant: Cn1c2c(c3ccc(-n4ccc(OCc5ccc(F)cc5)cc4=O)cc31)CN(C(=O)OC(C)(C)C)CCC2
Agent: Cl
Solvent: ClCCl
Product: Cn1c2c(c3ccc(-n4ccc(OCc5ccc(F)cc5)cc4=O)cc31)CNCCC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 38 %

Procedure:
To a solution of tert-butyl 8-(4-(4-fluorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H) carboxylate (120 mg, 0.23 mmol) in dichloromethane (1.0 mL) was added HCl (2M in diethyl ether, 5.0 mL). The resulting slurry was stirred at room temperature overnight and concentrated under reduced pressure. The residue was purified by semi-preparative HPLC (Phenomenex Luna C18 (2), 250.0×21.20 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA). The clean fractions were combined and concentrated under reduced pressure. The trifluoracetate salt was converted to HCl salt by dissolving in 1.25 M HCl in methanol and concentrating the resulting solution to dryness. This process was repeated three times to afford the title compound (40.0 mg, 38%) as an off-white solid: 1H NMR (500 MHz, CD3OD) δ 7.63 (d, J=8.5 Hz, 1H), 7.57 (d, J=7.5 Hz, 1H), 7.51 (dd, J=8.5, 5.5 Hz, 2H), 7.44 (s, 1H), 7.15 (t, J=8.5 Hz, 2H), 7.06 (dd, J=8.5, 2.0 Hz, 1H), 6.28 (dd, J=7.5, 3.0 Hz, 1H), 6.12 (d, J=3.0 Hz, 1H), 5.16 (s, 2H), 4.55 (s, 2H), 3.77 (s, 3H), 3.58 (t, J=5.5 Hz, 2H), 3.20 (t, J=5.5 Hz, 2H), 2.23-2.19 (m, 2H); ESI MS m/z 418 [M+H]+.
Reaction SMILES: [NH:1]1[C:9](=[O:10])[C:8]2[NH:7][CH:6]=[N:5][C:4]=2[N:3]=[CH:2]1.[CH2:11]([OH:13])[CH3:12]>N.[OH-].[OH-].[Pd+2]>[OH:13][C@@H:11]1[C@@H:8]([CH2:9][OH:10])[CH2:4][N:3]([N:5]2[CH:6]=[N:7][C:8]3[C:9](=[O:10])[NH:1][CH:2]=[N:3][C:4]2=3)[CH2:12]1
Reactant: CCO
Reactant: O=c1[nH]cnc2nc[nH]c12
Agent: [Pd+2]
Agent: N
Agent: [OH-]
Product: O=c1[nH]cnc2c1ncn2N1C[C@H](CO)[C@@H](O)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 88 %

Procedure:
tert-Butyl nitrite (3.5 mL, 30 mmol, 4 eq.) was added to a solution of the free base of 3 (2.25 g, 7.5 mmol) in dry THF (30 mL) and the reaction mixture was stirred at ambient temperature for 3 days. The solution was concentrated to dryness. Chromatography gave the N-nitroso compound 42 as a colorless syrup (2.05 g, 83%). A solution of 42 (1.0 g, 3.1 mmol) in dry THF (20 mL) was cooled to 0° C. under argon atmosphere and lithium aluminum hydride (1 g, 26.3 mmol) was added slowly. The mixture was stirred at room temperature for 6 h, then quenched carefully with a 15% solution of NaOH (25 mL) followed by water (10 mL). The mixture was extracted twice with chloroform, washed with aq NaHCO3 and dried and concentrated to dryness. Chromatography (chloroform:ethyl acetate:methanol, 5:2:1) afforded hydrazine 43 (0.41 g, 43%) as a syrup. Formimidate 44 (Watson, A. A. J. Org. Chem. 1974, 39, 2911-2916) (0.224 g, 1.44 mmol, 1.2 eq.) was added to a solution of 43 (0.375 g, 1.2 mmol) in ethanol (1.5 mL) and the reaction mixture was heated under reflux for 10 min, then allowed to cool. The solution was concentrated to dryness. Chromatography (chloroform:ethyl acetate:methanol, 5:2:1) gave the imidazole 45 as a light brown gum (0.155 g, 31%). A solution of 45 (77 mg, 0.183 mmol) in dry MeOH (1 mL) was treated with 5 M aq HCl (36.5 μL, 0.183 mmol). The solvent was removed to leave the hydrochloride salt as a brown gum. DMF (1.5 mL) was added followed by triethyl orthoformate (0.304 mL, 1.83 mmol, 10 eq.) and the reaction mixture was heated at 120° C. for 30 min. After cooling the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (chloroform:ethyl acetate:methanol, 5:2:0.5) to afford the hypoxanthine 46 (49 mg, 62%) as a gum. Palladium hydroxide on carbon (20 mg, 20% Pd) was added to a solution of 46 (41 mg, 0.095 mmol) in ethanol (3 mL) and 25% aqueous ammonia (1 mL). The reaction mixture was stirred under hydrogen at ambient temperature and pressure for 3 h. Then the catalyst was filtered off and washed with ethanol (1.5 mL). The solution was concentrated to dryness and chromatography of the residue (dichloromethane:methanol:aq. ammonia, 7:2:0.5) furnished the title compound 47 (21 mg, 88%) as a white solid. 1H NMR (CD3OD) δ 8.17 (s, 1H), 8.07 (s, 1H), 4.26 (m, 1H), 3.85-3.64 (m, 4H), 3.48-3.43 (m, 2H), 2.49-2.41 (m, 1H); 13C NMR δ 159.3 (C), 149.7 (C), 146.7 (CH), 142.3 (CH), 124.7 (C), 72.7 (CH), 63.7, 63.6, 58.4 (CH2), 50.2 (CH). M/Z calculated for C10H13N5O3 (MH+): 252.109. Found: 252.108.
Reaction SMILES: C([O:3][C:4](=[O:21])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH2:14][CH2:15][CH2:16][C:17]([F:20])([F:19])[F:18])[CH:6]=1)C.[OH-].[Na+].Cl>C1COCC1>[CH3:12][O:11][C:8]1[CH:9]=[CH:10][C:5]([C:4]([OH:21])=[O:3])=[CH:6][C:7]=1[O:13][CH2:14][CH2:15][CH2:16][C:17]([F:18])([F:20])[F:19]
Reactant: CCOC(=O)c1ccc(OC)c(OCCCC(F)(F)F)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COc1ccc(C(=O)O)cc1OCCCC(F)(F)F
Temperature: 60 °C
Reaction time: 8 h

Procedure:
A mixture of 4-methoxy-3-(4,4,4-trifluoro-butoxy)-benzoic acid ethyl ester (0.93 g, 3.04 mmol) in THF (3 mL) and 2N NaOH (2.28 mL, 4.55 mmol) is heated with stirring at 60° C. overnight. After cooling, ice water is added and the pH is adjusted to 1 by addition of HCl 37% to form a white precipitate which is filtered off. The title compound is obtained after drying as white solid. TLC, Rf (hexane/AcOEt 1:1)=0.17. MS: 277.0 [M−H]+. tR (HPLC, Nucleosil C18HD column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 3.90 min. 1H-NMR (CDCl3): δ 1.98 (m, 2H), 2.45 (m, 2H), 3.85 (s, 3H), 4.08 (m, 2H), 7.08 (dd, 1H), 7.46 (d, 1H), 7.60 (dd, 1H), 12.7 (s, br, 1H) ppm.
Reaction SMILES: [CH3:1][C:2](O)([C:4]#[CH:5])[CH3:3].C[O:8][C:9]([CH3:11])=[CH2:10].CC([O-])=O.[Na+]>C1(C=CC(O)=CC=1)O.FS(O)(=O)=O.CCCCCCC>[CH3:1][C:2]([CH3:3])=[C:4]=[CH:5][CH2:8][C:9](=[O:10])[CH3:11]
Reactant: C=C(C)OC
Reactant: C#CC(C)(C)O
Agent: CC(=O)[O-]
Agent: O=S(=O)(O)F
Agent: Oc1ccc(O)cc1
Solvent: CCCCCCC
Product: CC(=O)CC=C=C(C)C
Temperature: 68.5 °C
Yield: 87.5 %

Procedure:
25.3 g 2-methyl-3-butin-2-ol, 65.0 g isopropenyl methyl ether, 0.066 g hydroquinone and 120 ml n-heptane were initially introduced into a 500 ml flask under nitrogen. 15.0 mg fluorosulfonic acid were added, while stirring. The mixture was heated to the boiling point and stirred under reflux at 60 to 77° C. for 9 h. After cooling, it was neutralized with 2 ml methanolic NaOAc solution (10 g/1) and evaporated. After distillation, 32.7 g 6-methyl-4,5-heptadien-2-one were obtained, which corresponds to a yield of 87.86.
Reaction SMILES: [F:1][C:2]1[C:3]([CH2:35][O:36]S(C)(=O)=O)=[C:4]([F:34])[C:5]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[C:13]([F:24])[CH:12]=3)=[CH:8][C:7](=[O:25])[C:6]=2[C:26]=1[NH:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30].[CH3:41]O>>[F:1][C:2]1[C:3]([CH2:35][O:36][CH3:41])=[C:4]([F:34])[C:5]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[C:13]([F:24])[CH:12]=3)=[CH:8][C:7](=[O:25])[C:6]=2[C:26]=1[NH:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30]
Reactant: CC(C)(C)C(=O)Nc1ccc(-c2cc(=O)c3c(NC(=O)C(C)(C)C)c(F)c(COS(C)(=O)=O)c(F)c3o2)cc1F
Reactant: CO
Product: COCc1c(F)c(NC(=O)C(C)(C)C)c2c(=O)cc(-c3ccc(NC(=O)C(C)(C)C)c(F)c3)oc2c1F
Yield: 86 %

Procedure:
800 mg (1.37 mmol) of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methanesulfonyloxymethyl-5-pivaloylamino-4H-1-benzopyran-4-one obtained in Example 120 (1) was dissolved in 200 mL of methanol and the solution was heated at reflux for 24 hours. The solvent was distilled off under reduced pressure, the residue was dissolved in chloroform, washed once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (chloroform:acetonitrile=20:1) to give 610 mg of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-methoxymethyl-5-pivaloylamino-4H-1-benzopyran-4-one (yield: 86%).
Reaction SMILES: C1C(CC2C=CC(N)=CC=2)=CC=C(N)C=1.C1(=O)OCCC1.C1C(CC2C=CC(N=C=O)=CC=2)=CC=C(N=C=O)C=1.[CH:41]1[C:46]([C:47]([OH:49])=[O:48])=[CH:45][C:44]2C([O:52][C:53](=[O:54])[C:43]=2[CH:42]=1)=O.COC(=O)C1C=CC(C(OC)=O)=CC=1.C(=O)=O.OCC(CO)O>CCCC[O-].CCCC[O-].CCCC[O-].CCCC[O-].[Ti+4].C(O)(=O)C1C=CC=C(C(O)=O)C=1.C(O)(=O)C1C(=CC(=CC=1)C(O)=O)C(O)=O.N1CCNCC1.C([O-])(=O)C.[Pb+2].C([O-])(=O)C.C1(C)C(C)=CC=CC=1.C1(C)C=CC=CC=1.CO>[C:53]([OH:54])(=[O:52])[C:43]1[CH:42]=[CH:41][C:46]([C:47]([OH:49])=[O:48])=[CH:45][CH:44]=1
Reactant: O=C(O)c1ccc2c(c1)C(=O)OC2=O
Agent: [Ti+4]
Agent: C1CNCCN1
Agent: CC(=O)[O-]
Solvent: CO
Solvent: O=C1CCCO1
Solvent: OCC(O)CO
Product: O=C(O)c1ccc(C(=O)O)cc1
Temperature: 50 °C
Reaction time: 2 h

Procedure:
4.8 g of isophthalic acid and 33.6 g of trimellitic acid are added at room temperature to 419 g of a solution of N,N'-bis-[methoxy carbonyl propyl-(2)-]-4,4'-diaminodiphenyl methane in a mixture of 36% by weight of γ-butyrolactone and 64% by weight of toluene (29.2% N), followed by the addition at 50° C. of 204 g of 4,4'-diisocyanatodiphenylmethane. After stirring for 2 hours at 50° C., another 87.4 g of 4,4'-diisocyanatodiphenyl methane and 0.6 g of endoethylene piperazine are added at 50° C., followed by homogenisation for 1 hour at 50° C. Then another 201.2 g of trimellitic acid anhydride and 120 g of terephthalic acid dimethyl ester are added to this solution in portions at 50° C., followed by homogenisation for 30 minutes at 50° C. The suspension obtained is left standing overnight at room temperature and, on the following day, is heated to 205° C. with elimination of carbon dioxide, methanol and toluene, maintained for 3 hours at 205° C. and, then, for 1 hour at 215° C. 218.8 g of terephthalic acid dimethyl ester are then added at from 170° to 180° C., followed by the addition at from 150° to 160° C. of 318 g of N,N',N"-tris-hydroxyethyl triazolidine-3,5-dione, 1.8 g of lead acetate and 0.6 g of titanium tetrabutylate. The mixture is then heated for 2 hours to 170° C. Then 30 g of xylene and 160 g of a polyester produced from 4 moles of terephthalic acid, 1.5 moles of glycerol and 3 moles of glycol (OH-content 4.53%, acid number 4.8 mg KOH) are added at from 160° to 170° C., after which the mixture is again subjected to condensation for 3 hours at from 200° to 220° C. first directly and, finally, in vacuo until a sample diluted to 50% by weight with γ-butyrolactone has a viscosity of approximately 10,000 mPa.s at 25° C. 1501 g of a brittle, approximately 80% by weight resin are obtained, of which a 15% by weight solution in γ-butyrolactone has a viscosity of 156 mPa.s at 25° C.