Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:5]1[C:13]2[N:12]=[CH:11][N:10]([CH2:14][CH:15]=[CH2:16])[C:9]=2[C:8](=[O:17])[N:7]([CH3:18])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CN([CH:33]=[O:34])C>C1COCC1>[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([CH:33]=[O:34])[N:10]([CH2:14][CH:15]=[CH2:16])[C:9]=2[C:8](=[O:17])[N:7]([CH3:18])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]
Reactant: CN(C)C=O
Reactant: C=CCn1cnc2c1c(=O)n(C)c(=O)n2CCCC
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: C=CCn1c(C=O)nc2c1c(=O)n(C)c(=O)n2CCCC
Temperature: -75 °C
Yield: 105.8 %

Procedure:
A pre-dried flask was charged with 3-butyl-1-methyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (300 mg, 1.14 mmol) and anhydrous THF (6 ml), cooled to −75° C. under nitrogen, then treated with LiHMDS (1.37 ml of a 1.0M solution in THF). The resulting solution was allowed to warm to −60° C. over 1.5 hours before the addition of anhydrous DMF (177 ul, 2.29 mmol). The solution was allowed to warm to −10° C. over 3 hours then it was quenched with sat. NH4Cl (aq) solution. The mixture was partitioned between 1M HCl (aq) and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4) and concentrated giving a brown oil (350 mg). The product was purified by SPE (Si, 10 g) eluting with EtOAc/cyclohexane mixtures to give the title compound as a white solid (131 mg, 39%); NMR; δH (400 MHz, d6-DMSO) 0.91 (t, 3H, J=7.5 Hz), 1.28-1.39 (m, 2H), 1.63-1.73 (m, 2H), 3.25 (s, 3H), 4.02 (t, 2H, J=7.5 Hz), 5.03 (dd, 1H, J=17 and 1 Hz), 5.17 (dd, 1H, J=10 and 1 Hz), 5.31 (app. d, 2H, J=5.5 Hz), 5.98-6.09 (m, 1H), 9.88 (s, 1H).
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[Br:13][C:14]1[CH:15]=[C:16]([CH:20]([CH3:24])[C:21]([OH:23])=[O:22])[CH:17]=[N:18][CH:19]=1.[F:25][C:26]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:27]=1[CH:28]=[O:29]>O1CCCC1>[Br:13][C:14]1[CH:15]=[C:16]([C:20]([CH3:24])([CH:28]([C:27]2[CH:30]=[C:31]([F:34])[CH:32]=[CH:33][C:26]=2[F:25])[OH:29])[C:21]([OH:23])=[O:22])[CH:17]=[N:18][CH:19]=1
Reactant: O=Cc1cc(F)ccc1F
Reactant: CC(C(=O)O)c1cncc(Br)c1
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CC(C(=O)O)(c1cncc(Br)c1)C(O)c1cc(F)ccc1F
Temperature: -15 °C
Reaction time: 0.17 h

Procedure:
In a flame dried flask under nitrogen was added diisopropylamine (0.976 mL, 6.85 mmol), tetrahydrofuran (4 mL) and the vessel was cooled to −78° C. n-BuLi (2.74 mL, 6.85 mmol) was added dropwise and after 10 min, the reaction was warmed to −15° C. and held there for 10 min before recooling to −78° C. 2-(5-bromopyridin-3-yl)propanoic acid (750 mg, 3.26 mmol) held in a flame dried flask was dissolved in tetrahydrofuran (4 mL) and added dropwise to the preformed LDA resulting in a kool-aid orange solution. The ice bath was again removed and the reaction was allowed to stir at ambient temperature for 1.5 h, recooled to −78° C. and 2,5-difluorobenzaldehyde (0.779 mL, 7.17 mmol) in 2 mL tetrahydrofuran was added over 10 min. After 1 h, the reaction was quenched with 10% citric acid and the volatiles were removed under vacuum. The residue was extracted with 3 portions ether, washed with brine, dried over MgSO4, filtered and concentrated to 1.31 g red gum which was used immediately in the next step.
Reaction SMILES: [CH3:1][NH:2][CH3:3].[F:4][P-:5]([F:10])([F:9])([F:8])([F:7])[F:6].Cl/[C:12](/[C:18]1[CH:19]=[N:20][N:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=12)=[CH:13]\[CH:14]=[N+:15]([CH3:17])[CH3:16]>CO>[F:4][P-:5]([F:10])([F:9])([F:8])([F:7])[F:6].[CH3:1][N:2]([CH3:3])/[C:12](/[C:18]1[CH:19]=[N:20][N:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=12)=[CH:13]\[CH:14]=[N+:15]([CH3:17])[CH3:16]
Reactant: CNC
Reactant: C[N+](C)=C/C=C(\Cl)c1cnn2ccccc12
Agent: F[P-](F)(F)(F)(F)F
Solvent: CO
Product: CN(C)/C(=C\C=[N+](C)C)c1cnn2ccccc12
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 85.1 %

Procedure:
Dimethylamine (24.0 mL, 48.0 mmol, 2M in THF) was added in one portion to a suspension of (Z)—N-(3-chloro-3-(pyrazolo[1,5-a]pyridin-3-yl)allylidene)-N-methylmethanaminium hexafluorophosphate (Intermediate 71, 6.07 g, 16 mmol) in CH3OH (40 mL) at r.t. under N2. The resulting solution was stirred at r.t. for 0.25 h then stored in the freezer overnight. Crystals were produced and these were collected, washed with CH3OH at −50° C. and THF, then dried by suction under a stream of N2. Two crops of crystals were collected to give the title compound (5.29 g, 85%) as a beige crystalline solid; m/z: ES+ M+ 244.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][C:5]([CH3:9])([CH3:8])[CH2:6][OH:7].[O:10]1[CH:15]=[CH:14][CH2:13][CH2:12][CH2:11]1>C(Cl)Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][CH2:2][CH2:3][CH2:4][C:5]([CH3:9])([CH3:8])[CH2:6][O:7][CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15][O:10]1
Reactant: CC(C)(CO)CCCBr
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: CC(C)(CCCBr)COC1CCCCO1
Yield: 90.4 %

Procedure:
According to the procedure for the preparation of 207d, 206a (78.0 g, 0.40 mol) was reacted with 3,4-dihydro-2H-pyran (41.5 g, 0.49 mol) and p-toluenesulfonic acid hydrate (0.42 g, 2.2 mmol) in CH2Cl2 (0.5 L) to yield 207a (101.0 g, 90%) as a pale-yellow oil, which was used without further purification. 1H NMR (CDCl3): δ 4.55 (t, 1H, J=2.9), 3.83 (m, 1H), 3.51 (m, 1H), 3.47 (d, 1H, J=9.0), 3.38 (t, 2H, J=6.8), 2.98 (d, 1H, J=9.0), 1.94-1.75 (m, 2H), 1.75-1.44 (m, 6H), 1.40 (t, 2H, J=8.5), 0.91 (s, 3H), 0.90 (s, 3H). 13C NMR (CDCl3): δ 99.01, 76.17, 61.85, 37.89, 34.66, 34.04, 30.62, 27.92, 25.60, 24.64, 24.56, 19.41. HRMS (LSIMS, nba): Calcd for C12H24BrO2 (MH+): 279.0960, found: 279.0955.
Reaction SMILES: [Br:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH2:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CN(C)C=O.CN1CCCC1=O>[CH2:32]([NH:39][C:8]([C:4]1[S:3][C:2]([Br:1])=[N:6][C:5]=1[CH3:7])=[O:10])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: NCc1ccccc1
Reactant: Cc1nc(Br)sc1C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN1CCCC1=O
Solvent: CN(C)C=O
Product: Cc1nc(Br)sc1C(=O)NCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture consisting of 2-bromo-4-methylthiazole-5-carboxylic acid (Sigma-Aldrich, 1.0 g), 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide (EDC, 1.3 g), 1-hydroxybenzotriazole (0.613 g), N-methyl-2-pyrrolidinone (0.48 mL) in N,N-dimethylformamide was added a mixture consisting of benzylamine (0.54 mL) in N,N-dimethylformamide (5 mL). The reaction mixture was stirred overnight at room temperature and was subsequently partitioned between ethyl acetate (200 mL) and water (200 mL). The layers were separated and the organic phase was further washed twice with water (2×200 mL) and brine solution (150 mL), was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure afforded the title intermediate as a crude yellow oil (1.847 g; major spot Rf 0.45 with 3:1 v/v hexanes-ethyl acetate solvent system) that solidified on standing at room temperature; MS (ESI−) m/z 311.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:14]3[CH:15]=[N:16][CH:17]=[CH:18][C:13]=3[N:12]([C:19]([CH3:30])([CH3:29])[CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[NH3:31]>CN1C(=O)CCC1>[NH2:31][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:14]3[CH:15]=[N:16][CH:17]=[CH:18][C:13]=3[N:12]([C:19]([CH3:30])([CH3:29])[CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1
Reactant: N
Reactant: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(Br)c2)c2cnccc21
Solvent: CN1CCCC1=O
Product: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(N)c2)c2cnccc21
Temperature: 80 °C
Reaction time: 18 h
Yield: 57 %

Procedure:
To a solution of (5-bromopyridin-3-yl)[1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]methanone (Preparation 43, 643 mg, 1.32 mmol) in NMP (1 mL) was added Cu2O (18.9 mg, 0.132 mmol) and 880 ammonia (6 mL) and the reaction heated to 80° C. in a Reactivial™ for 18 hours followed by an additional 18 hours at 90° C. The reaction was cooled and partitioned between water (15 mL) and EtOAc (20 mL). The aqueous layer was extracted twice with EtOAc (2×20 mL), the organic layers combined, dried and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 50:50 DCM:EtOAc to 80:20 EtOAc:MeOH to afford the title compound as a yellow gum (320 mg, 57%).
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.Cl[CH2:16][CH2:17][N:18]([CH2:21][CH3:22])[CH2:19][CH3:20].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:17]([N:18]([CH2:21][CH3:22])[CH2:19][CH2:20][N:12]1[CH:13]=[C:9]([B:4]2[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]2)[CH:10]=[N:11]1)[CH3:16]
Reactant: CCN(CC)CCCl
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCN(CC)CCn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Temperature: 140 °C
Reaction time: 1.5 h
Yield: 13.6 %

Procedure:
To a solution of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (500 mg, 2.5 mmol) in DMF (10 mL) was added (2-chloroethyl)diethylamine (Compound 175B, 0.6 g, 4 mmol) and K2CO3 (1.38 g, 10 mmol). The reaction mixture was stirred at 140° C. for 1.5 h in a microwave reactor, then concentrated, residue was purified by HPLC to afford 100 mg of the title compound (yield: 12%). 1H NMR (DMSO-d6, 400 MHz): δ=1.1-1.2 (m, 9H), 1.25 (s, 12H), 2.72 (s, 0.5H), 2.75 (s, 1H), 3.00-3.10 (s, 4H), 3.1-3.2 (m, 2H), 3.44 (s, 3H), 4.58-4.59 (br, 3H), 7.74 (s, 1H), 7.82 (s, 0.5H), 8.05 (s, 0.5H), 8.09 (s, 1H).
Reaction SMILES: [F:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[CH:13][C:8]=2[C:9]([O:11][CH3:12])=[O:10])=[CH:4][C:3]=1[NH:22][C:23](=[O:35])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=1.O1CCCC1>CO.[C].[Pd]>[NH2:17][C:14]1[CH:15]=[CH:16][C:7]([O:6][C:5]2[CH:20]=[CH:21][C:2]([F:1])=[C:3]([NH:22][C:23](=[O:35])[CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:32])[F:33])[CH:26]=3)[CH:4]=2)=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10]
Reactant: COC(=O)c1cc([N+](=O)[O-])ccc1Oc1ccc(F)c(NC(=O)Cc2cccc(C(F)(F)F)c2)c1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)c1cc(N)ccc1Oc1ccc(F)c(NC(=O)Cc2cccc(C(F)(F)F)c2)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 87.7 %

Procedure:
To a solution of methyl 2-[4-fluoro-3-({[3-(trifluoromethyl)phenyl]acetyl}amino)phenoxy]-5-nitrobenzoate (3.75 g, 7.62 mmol) in methanol (40 mL)/tetrahydrofuran (8 mL) solution was added 10% palladium-carbon (400 mg), and the mixture was stirred at room temperature for 6 hr under a hydrogen atmosphere (1 atm). Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=30/70→80/20), and the fraction containing the object product was concentrated under reduced pressure to give the title compound (3.09 g, 87%) as a yellow oil.
Reaction SMILES: O1[CH2:5][CH2:4][CH2:3][CH2:2]1.[H][H]>[Pd].[C].C1(C)C=CC=CC=1>[C:2]1([C:3]2[CH:2]=[CH:5][CH:4]=[CH:5][CH:4]=2)[CH:3]=[CH:2][CH:5]=[CH:4][CH:3]=1
Reactant: C1CCOC1
Reactant: [H][H]
Agent: [Pd]
Solvent: Cc1ccccc1
Product: c1ccc(-c2ccccc2)cc1

Procedure:
1.31 g (3 mmol) of II-23 was mixed with 10 ml of tetrahydrofuran, 3 ml of toluene and 0.1 g of 2% Pd-carbon, and the mixture was subjected to catalytic hydrogenation in a hydrogen atmosphere. The reaction mixture was filtered to remove the catalyst and further treated and purified according to Example 21 to obtain 0.32 g (31% yield) of (+)-4-hydroxy-4'-(1-2's,3's-2-chloro-3-methylpentanoyl)ethyl)biphenyl. [α]D25 =+60° (c=1, CHCl3), m.p.=99°-100° C.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]3[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@H:21]([CH2:31][OH:32])[CH2:20]3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH2:33]([C:35]1[CH:40]=[CH:39][C:38]([N:41]=[C:42]=[O:43])=[CH:37][CH:36]=1)[CH3:34]>CN(C1C=CN=CC=1)C.C1COCC1>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]3[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[C@H:21]([CH2:31][O:32][C:42](=[O:43])[NH:41][C:38]4[CH:39]=[CH:40][C:35]([CH2:33][CH3:34])=[CH:36][CH:37]=4)[CH2:20]3)=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1
Reactant: CC(C)(C)OC(=O)N1C[C@H](NC(=O)OCC2c3ccccc3-c3ccccc32)C[C@H]1CO
Reactant: CCc1ccc(N=C=O)cc1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CCc1ccc(NC(=O)OC[C@@H]2C[C@@H](NC(=O)OCC3c4ccccc4-c4ccccc43)CN2C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (2S,4R)-tert-butyl 4-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (403 mg, 0.92 mmol) and DMAP (134 mg, 1.1 mmol) in THF (10 mL) was added 4-ethylphenyl isocyanate (162 mg, 11 mmol). The reaction mixture was stirred at rt overnight and concentrated to give (2S,4R)-tert-butyl 4-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-((4-ethylphenylcarbamoyloxy)methyl)pyrrolidine-1-carboxylate, which was used without further purification. LRMS (M+H+) m/z 585.1.
Reaction SMILES: [C:1]1([CH:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:8]2[CH2:11][CH:10](OS(C)(=O)=O)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:23][NH:24][S:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)(=[O:27])=[O:26].C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1>[C:17]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[CH2:9][CH:10]([N:24]([CH3:23])[S:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)(=[O:27])=[O:26])[CH2:11]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CS(=O)(=O)OC1CN(C(c2ccccc2)c2ccccc2)C1
Reactant: CNS(=O)(=O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1COCCO1
Product: CN(C1CN(C(c2ccccc2)c2ccccc2)C1)S(=O)(=O)c1ccccc1
Temperature: 25 °C
Yield: 75.7 %

Procedure:
To a solution of 1-diphenylmethyl-3-methanesulphonyloxyazetidine (WO 96/05193) (1.4 g) in dioxane (25 mL) were added N-methyl benzenesulphonamide (1.2 g) and caesium carbonate (2.6 g). The reaction mixture was heated to reflux for 3 h, then cooled to room temperature. Water (20 mL) was added to the resulting slurry, and the mixture was extracted with ethyl acetate (3×25 mL). The combined organics were washed with brine, dried over magnesium sulphate, filtered and dried in vacuo to yield crude product. Chromatography on silica gel eluting with ethyl acetate:hexanes (2:3 by volume) yielded the title compound as a white foam (1.31 g).
Reaction SMILES: [N+:1]([C:4]1[O:8][C:7]([C:9]2[C:13]([C:14]#[N:15])=[CH:12][N:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].S(=O)(=O)(O)[OH:23]>O>[N+:1]([C:4]1[O:8][C:7]([C:9]2[C:13]([C:14]([NH2:15])=[O:23])=[CH:12][N:11]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: N#Cc1cn(-c2ccccc2)nc1-c1ccc([N+](=O)[O-])o1
Reactant: O=S(=O)(O)O
Solvent: O
Product: NC(=O)c1cn(-c2ccccc2)nc1-c1ccc([N+](=O)[O-])o1
Temperature: 40 °C
Yield: 98 %

Procedure:
Add 29.4 g of 3-(5-nitro-2-furyl)-1-phenylpyrazole-4-carbonitrile to 59 ml of concentrated sulfuric acid while stirring and maintaining the temperature at 40° C for 5 hours. Pour the solution onto 500 g of ice and water. Seperate the formed precipitate by vacuum filtration and wash it with water until it is neutral to obtain a 98% yield of 3-(5-nitro-2-furyl)-1-phenylpyrazole-4-carboxamide [m.p. 236° to 238° C (from dimethylformamide/methanol)].
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:13][CH3:14])[C:11]=1[F:12])[N:8]([CH2:15][C:16]([F:19])([F:18])[F:17])[CH:7]=[C:6]([C:20]([O:22]CC)=[O:21])[C:5]2=[O:25]>C(O)(=O)C.O.S(=O)(=O)(O)O>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:13][CH3:14])[C:11]=1[F:12])[N:8]([CH2:15][C:16]([F:19])([F:17])[F:18])[CH:7]=[C:6]([C:20]([OH:22])=[O:21])[C:5]2=[O:25]
Reactant: CCOC(=O)c1cn(CC(F)(F)F)c2c(OC)c(F)c(F)cc2c1=O
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: O
Product: COc1c(F)c(F)cc2c(=O)c(C(=O)O)cn(CC(F)(F)F)c12

Procedure:
800 mg (2.19 mmol) of the compound of Example 23A are provided in a mixture of 25 ml of acetic acid-water-sulfuric acid 12:8:1 and stirred over night under reflux. For the work-up the solvent is removed to a large extent on a rotary evaporator, the residue is adjusted carefully to pH 3 while cooling with ice with a saturated sodium hydrogen carbonate solution, the suspension is diluted with water, the precipitate is collected by suction filtration and after drying the filter residue under high vacuum, 575 mg of the title compound are obtained.
Reaction SMILES: [CH2:1]([N:4]=[C:5]([C:7]1[C:24]2=[C:25]3[C:14]([C:15]4[C:26]5[C:19](=[CH:20][CH:21]=[CH:22][C:23]2=5)[CH:18]=[CH:17][CH:16]=4)=[CH:13][CH:12]=[C:11]([C:27]([OH:29])=[O:28])[C:10]3=[C:9]([C:30]([OH:32])=[O:31])[C:8]=1[C:33](=[N:35][CH2:36][CH:37]=[CH2:38])[OH:34])[OH:6])[CH:2]=[CH2:3].[CH3:39][Si:40]([CH3:50])([CH3:49])[O:41][Si:42]([CH3:48])([CH3:47])[O:43][SiH:44]([CH3:46])[CH3:45]>C1(C)C=CC=CC=1>[CH3:39][Si:40]([CH3:49])([CH3:50])[O:41][Si:42]([CH3:48])([CH3:47])[O:43][Si:44]([CH2:3][CH2:2][CH2:1][N:4]=[C:5]([C:7]1[C:24]2=[C:25]3[C:14]([C:15]4[C:26]5[C:19](=[CH:20][CH:21]=[CH:22][C:23]2=5)[CH:18]=[CH:17][CH:16]=4)=[CH:13][CH:12]=[C:11]([C:27]([OH:29])=[O:28])[C:10]3=[C:9]([C:30]([OH:32])=[O:31])[C:8]=1[C:33](=[N:35][CH2:36][CH2:37][CH2:38][Si:44]([CH3:46])([CH3:45])[O:43][Si:42]([CH3:48])([CH3:47])[O:41][Si:40]([CH3:50])([CH3:49])[CH3:39])[OH:34])[OH:6])([CH3:45])[CH3:46]
Reactant: C=CCN=C(O)c1c(C(=O)O)c2c(C(=O)O)ccc3c4cccc5cccc(c(c1C(O)=NCC=C)c23)c54
Reactant: C[SiH](C)O[Si](C)(C)O[Si](C)(C)C
Solvent: Cc1ccccc1
Product: C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)CCCN=C(O)c1c(C(=O)O)c2c(C(=O)O)ccc3c4cccc5cccc(c(c1C(O)=NCCC[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C)c23)c54
Yield: 75.3 %

Procedure:
1.03 g (2.19 mmol) of perylene tetracarboxylic acid bis(allylimide) (compound (6), m=1, n=1) and 1.53 g (6.87 mmol) of 1,1,1,3,3,5,5-heptamethyl trisiloxane were dissolved in 100 ml of toluene, and 20 μl of a Karstedt catalyst (2 mol/l solution in xylene) was thereafter added thereto, which was then refluxed for 5 hours. The reaction solution thus obtained was then cooled and filtered, and the toluene was distilled off from a filtrate. The crude product thus obtained was purified by silica gel column chromatography (eluent: dichloromethane→dichloromethane-ethyl acetate (50:1)). The resultant crude product was dissolved in dichloromethane and re-precipitated with methanol. Thus, 1.51 g (1.65 mmol) of a red powder was obtained as an intended compound (1-1). A yield of the compound (1-1) was 75.3%. Values obtained by instrumental analysis of the compound (1-1) are shown below.
Reaction SMILES: CN1CCCN(C)C1=O.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=1[CH2:18][S:19]([C:22]1[CH2:26][C:25]([CH3:28])([CH3:27])[O:24][N:23]=1)(=[O:21])=[O:20].C([Li])CCC.[I:34]N1C(=O)CCC1=O>C1COCC1>[F:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([F:10])[C:12]=1[CH:18]([I:34])[S:19]([C:22]1[CH2:26][C:25]([CH3:28])([CH3:27])[O:24][N:23]=1)(=[O:20])=[O:21]
Reactant: O=C1CCC(=O)N1I
Reactant: CC1(C)CC(S(=O)(=O)Cc2c(F)cccc2F)=NO1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CN1CCCN(C)C1=O
Product: CC1(C)CC(S(=O)(=O)C(I)c2c(F)cccc2F)=NO1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 38.4 %

Procedure:
1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone (DMPU) (0.10 ml, 0.83 mmol) and 3-(2,6-difluoro-phenylmethanesulfonyl)-5,5-dimethyl-4,5-dihydro-isoxazole (0.20 g, 0.69 mmol) were dissolved under nitrogen in THF (7 ml) and cooled to −78° C. n-Butyl lithium (2.5M in hexane) (0.33 ml, 0.83 mmol) was added dropwise. After 30 min at −78° C., N-iodosuccinimide (NIS) (187 mg, 0.83 mmol) was added. The mixture was stirred for 1 hour and allowed to warm slowly to room temperature. The reaction was quenched by addition of aqueous ammonium chloride solution. Extraction was carried out several times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated. The crude product was purified by chromatography on silica gel (eluent: ethyl acetate/hexane) and recrystallised from isopropyl alcohol to give the product (Compound No. 1.25 of Table 27) as a white solid (110 mg, 38% yield).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:19]([N:20]([CH3:24])[CH:21]([CH3:23])[CH3:22])=[N:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:25]([O:27]C)=[O:26])[CH:16]=2)[N:11]=1.[OH-].[Na+].Cl>CO.O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:19]([N:20]([CH3:24])[CH:21]([CH3:23])[CH3:22])=[N:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:25]([OH:27])=[O:26])[CH:16]=2)[N:11]=1
Reactant: COC(=O)c1ccc2nc(-c3nc4ccccc4s3)c(N(C)C(C)C)nc2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)N(C)c1nc2cc(C(=O)O)ccc2nc1-c1nc2ccccc2s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 39.4 %

Procedure:
To a solution of methyl 2-(1,3-benzothiazol-2-yl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylate (50 mg, 0.13 mmol) in methanol (30 mL), was added sodium hydroxide (50 mg, 1.25 mmol). After stirring overnight at room temperature, the reaction mixture was concentrated under reduced pressure to afford a residue, which was dissolved in water (10 mL), adjusted the pH value to 6 with 3 N HCl and filtered to give 2-(1,3-benzothiazol-2-yl)-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylic acid as a light yellow solid (19.4 mg, 40%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH:5]=[O:6].[C-:11]#[N:12].[K+]>O>[F:1][C:2]1[CH:3]=[C:4]([CH:5]([OH:6])[C:11]#[N:12])[CH:7]=[CH:8][C:9]=1[F:10]
Reactant: O=Cc1ccc(F)c(F)c1
Reactant: [C-]#N
Agent: [K+]
Solvent: O
Product: N#CC(O)c1ccc(F)c(F)c1
Temperature: 50 °C
Reaction time: 1 h
Yield: 80.7 %

Procedure:
A solution of 80.2 g of Na2S2O5 in 250 ml of water is heated to 50° C., 50 g of 3,4-difluorobenzaldehyde are added and the reaction mixture is stirred for 1 hour at 50° C. and left to stand overnight at RT. It is cooled to 0° C., a solution of 77.7 g of KCN in 100 ml of water is added dropwise, the mixture is stirred while the temperature is allowed to rise to RT, and stirring is then continued for 1 hour at RT. The reaction mixture is extracted with ether, the organic phase is washed with water and dried over MgSO4 and the solvent is evaporated off under vacuum to give 48 g of the expected product, which is used as such.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH:14]([OH:28])[CH2:15][S:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)=[CH:4][CH:3]=1.[CH2:29]([O:31][C:32]([C:34]1([C:37]2[CH:42]=[CH:41][C:40](B3OC(C)(C)C(C)(C)O3)=[CH:39][CH:38]=2)[CH2:36][CH2:35]1)=[O:33])[CH3:30]>>[CH2:29]([O:31][C:32]([C:34]1([C:37]2[CH:42]=[CH:41][C:40]([C:2]3[CH:3]=[CH:4][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[CH:14]([OH:28])[CH2:15][S:16][CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:26])([F:27])[F:25])[CH:19]=4)=[CH:6][CH:7]=3)=[CH:39][CH:38]=2)[CH2:35][CH2:36]1)=[O:33])[CH3:30]
Reactant: Cc1noc(-c2ccc(Br)cc2)c1C(O)CSCc1cccc(C(F)(F)F)c1
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4C(O)CSCc4cccc(C(F)(F)F)c4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 2, using 1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-2-(3-trifluoromethyl-benzylsulfanyl)-ethanol and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester.