Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[S:10](Cl)(=[O:12])=[O:11].C(OC(=O)[NH:20][OH:21])(C)(C)C.C(N([CH2:28][CH3:29])CC)C>C(OCC)C>[NH2:20][O:21][S:10]([C:3]1[C:4]([CH3:9])=[CH:5][C:6]([CH3:8])=[CH:7][C:28]=1[CH3:29])(=[O:11])=[O:12]
Reactant: CCN(CC)CC
Reactant: Cc1cc(C)c(S(=O)(=O)Cl)c(C)c1
Reactant: CC(C)(C)OC(=O)NO
Solvent: CCOCC
Product: Cc1cc(C)c(S(=O)(=O)ON)c(C)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 58.7 %

Procedure:
To a stirred solution of 25.0 grams (114 mmole) of 2,4,6-trimethyl-benzenesulfonyl chloride, 15.2 grams (114 mmole) of t-butyl-N-hydroxy-carbamate, and 350 mL of diethyl ether, cooled in an ice bath, was added dropwise 11.4 grams (114 mmole) of triethylamine. Upon completion of the addition the reaction mixture was stirred at ambient temperature for about 18 hours, then filtered, and the filtrate was concentrated under reduced pressure. The concentrate was taken up in toluene and petroleum ether, filtered, and 150 mL of trifluoroacetic acid was added. The reaction mixture was stirred for 1.5 hours in an ice bath, then poured into ice-water, filtered, and extracted with diethyl ether. The organic extract was dried with magnesium sulfate and filtered. Petroleum ether was added to the filtrate, and the resulting precipitate was collected by filtration, yielding 14.4 grams of 1-aminooxysulfonyl-2,4,6-trimethylbenzene. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>COCCOC>[C:12]1([C:2]2[CH:10]=[C:9]3[C:5]([CH2:6][C:7](=[O:11])[NH:8]3)=[CH:4][CH:3]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C1Cc2ccc(Br)cc2N1
Reactant: OB(O)c1ccccc1
Solvent: COCCOC
Product: O=C1Cc2ccc(-c3ccccc3)cc2N1
Yield: 47.2 %

Procedure:
6-Bromooxindole (800 mg, 3.8 mmol), (prepared as described for the starting material in Example 62), phenylboronic acid (500 mg, 4.1 mmol) sodium hydrogen carbonate (saturated aqueous solution, 50 ml) and 1,2-dimethoxyethane (100 ml) were mixed together and the solution was degassed using alternatively vacuum and argon. Tetrakis(triphenylphosphine)palladium(0) (50 mg) was added and the solution degassed again before heating it to reflux for 8 hours. The reaction mixture was evaporated to dryness using a rotary evaporator and the solid residue partitioned between water (75 ml) and ethyl acetate (100 ml). The aqueous phase was reextracted with more ethyl acetate (100 ml×3), the organic phases were combined, washed with brine and passed directly through a short plug of silica to remove the baseline impurities. The solvent was evaporated and the solid was triturated in ether and filtered to give 6-phenyloxindole as a pink solid (375 mg, 60%).
Reaction SMILES: [NH:1]1[C:9]2[CH2:8][C@@H:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][CH2:5][C:4]=2[N:3]=[CH:2]1.CO>O1CCOCC1.O=[Mn]=O>[CH3:13][O:12][C:10]([C:7]1[N:6]=[CH:5][C:4]2[N:3]=[CH:2][NH:1][C:9]=2[CH:8]=1)=[O:11]
Reactant: COC(=O)[C@@H]1Cc2[nH]cnc2CN1
Agent: O=[Mn]=O
Solvent: C1COCCO1
Solvent: CO
Product: COC(=O)c1cc2[nH]cnc2cn1

Procedure:
A mixture of 59.9 g methyl (6S)-4,5,6,7-tetrahydro-imidazo[4,5-c]pyridine-6-carboxylate and 172.5 g MnO2 in 2 l anhydrous 1,4-dioxane is refluxed for 4 hours. The reaction mixture is allowed to come to 60-70° C. whereupon 1 l methanol is slowly added. The suspension is filtered hot and the filtrate is concentrated under reduced pressure to give a first batch of the title product. The filter cake is washed with hot methanol (2 l) and concentrated under reduced pressure to a volume of about 50 ml. 80 ml 1,4-dioxane is added whereupon precipitation takes place. After filtration a second batch of the title product is obtained. The washing procedure of the initial filter cakes is repeated once again to give a third batch of the title product.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:5]2[N:6]=[CH:7][S:8][C:4]=2[CH:3]=1.[C:11](=[O:14])([O-])[O-].[Na+].[Na+].[CH2:17]1[CH2:21]O[CH2:19][CH2:18]1>C(Cl)(Cl)Cl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:7][N:6]1[C@H:5]2[C@@:17]([CH3:21])([C:17]3[CH:21]=[CH:10][C:2]([C:2]4[CH:10]=[CH:9][C:5]5[N:6]=[CH:7][S:8][C:4]=5[CH:3]=4)=[CH:3][C:18]=3[CH2:19][CH2:4]2)[CH2:18][CH2:19][C:11]1=[O:14]
Reactant: O=C([O-])[O-]
Reactant: C1CCOC1
Reactant: Brc1ccc2ncsc2c1
Agent: [Pd]
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClC(Cl)Cl
Product: CN1C(=O)CC[C@]2(C)c3ccc(-c4ccc5ncsc5c4)cc3CC[C@@H]12
Yield: 47 %

Procedure:
A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one-8-boronic acid(178 mg, 0.65 mmol), tetrakis (triphenylphosphine) palladium (0) (23 mg, 0.02 mmol), 6-bromobenzothiazole (139 mg, 0.65 mmol), 0.65 mL of 2M aqueous sodium carbonate and 2 mL of THF, fitted with a reflux condenser, and the stirred mixture was heated at 80°, under nitrogen, for 24 h. The mixture was cooled, diluted with chloroform (75 mL) and washed with brine (2×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (20% ethyl acetate/hexanes eluent) to give 106 mg (47%) of the title compound as an amorphous solid. mp 183°-187°. FDMS: m/e=362. α[D]589 =+87.80 (c=0.55, chloroform).
Reaction SMILES: C([O:3][C:4](=[O:40])[CH:5]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:6][CH2:7][CH:8]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:9]([O:11]CC)=[O:10])C.[OH-].[K+]>O.CO>[C:34]1([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH2:27][CH:5]([CH2:6][CH2:7][CH:8]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:9]([OH:11])=[O:10])[C:4]([OH:40])=[O:3])[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: CCOC(=O)C(CCC(Cc1ccccc1-c1ccccc1)C(=O)OCC)Cc1ccccc1-c1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)C(CCC(Cc1ccccc1-c1ccccc1)C(=O)O)Cc1ccccc1-c1ccccc1
Yield: 85 %

Procedure:
To the 2,5-bis(2-phenyl-benzyl) adipic acid diethylester, obtained as described above, were added 180 mL of a solution of 6M KOH in H2O/MeOH and the reaction mixture was refluxed for 16 hours. MeOH was removed on a rotary evaporator and the aqueous layer was washed with Et2O (2×200 mL). The alkaline aqueous layer was acidified, at 0° C., with HCl 37% to pH 1. A white/yellow powder was formed, filtered off and washed with water and a little hexane. Said powder was thoroughly dried, to afford 77.0 g of 2,5-bis(2-phenyl-benzyl) adipic acid (85% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[C:8]([CH2:19][NH2:20])=[CH:7]2.Cl[C:22]1[N:27]=[C:26]([O:28][CH3:29])[NH:25][C:24]2=[N:30][CH:31]=[CH:32][C:23]=12.CCN(C(C)C)C(C)C>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[C:8]([CH2:19][NH:20][C:22]1[C:23]3[CH:32]=[CH:31][NH:30][C:24]=3[N:25]=[C:26]([O:28][CH3:29])[N:27]=1)=[CH:7]2
Reactant: COc1nc(Cl)c2ccnc-2[nH]1
Reactant: NCc1cc2cccc(Cl)c2nc1-c1ccccc1Cl
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: COc1nc(NCc2cc3cccc(Cl)c3nc2-c2ccccc2Cl)c2cc[nH]c2n1

Procedure:
Prepared according to Procedure H using (8-chloro-2-(2-chlorophenyl)quinolin-3-yl)methanamine (0.100 g, 0.33 mmol), 4-chloro-2-methoxy-pyrrolo[2,3-d]pyrimidine (0.061 g, 0.33 mmol, 1 eq) and DIEA (0.07 mL, 0.4 mmol, 1.2 eq) in ethanol (3 mL). N-((8-Chloro-2-(2-chlorophenyl)quinolin-3-yl)methyl)-2-meth-oxy-7H-pyrrolo[2,3-d]pyrimidin-4-amine [PI3Kδ IC50=5420 nM] was obtained after purification as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.28 (1 H, s), 8.37 (1 H, s), 8.03 (1 H, dd, J=8.4, 1.0 Hz), 7.94-7.99 (1 H, m), 7.94 (1 H, dd, J=7.6, 1.4 Hz), 7.40-7.65 (5 H, m), 6.88 (1 H, dd, J=3.3, 2.2 Hz), 6.47 (1 H, s), 4.59 (2 H, s), 3.67 (3 H, s) Mass Spectrum (ESI) m/e=450.1 and 452.0 (M+1)
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][CH3:16])[C:11]([C:17]([F:20])([F:19])[F:18])=[CH:10][C:9]=1[NH:21][C:22](=[O:42])[CH2:23][C:24](=O)[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]2[CH:36]=[CH:35][N:34]=C(C(F)(F)F)[CH:32]=2)[CH:26]=1)(C)(C)C.[C:44](O)([C:46]([F:49])([F:48])[F:47])=O>C(Cl)Cl>[CH2:15]([O:14][C:12]1[C:11]([C:17]([F:20])([F:19])[F:18])=[CH:10][C:9]2[NH:21][C:22](=[O:42])[CH2:23][C:24]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]4[CH:36]=[CH:35][N:34]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:32]=4)[CH:26]=3)=[N:7][C:8]=2[CH:13]=1)[CH3:16]
Reactant: O=C(O)C(F)(F)F
Reactant: CCOc1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-c3ccnc(C(F)(F)F)c3)c2)cc1C(F)(F)F
Solvent: ClCCl
Product: CCOc1cc2c(cc1C(F)(F)F)NC(=O)CC(c1cccc(-c3ccnc(C(F)(F)F)c3)c1)=N2

Procedure:
The title compound was prepared from (5-ethoxy-2-{3-oxo-3-[3-(2-trifluoromethyl-pyridin-4-yl)-phenyl]-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M248) (0.30 g, 0.49 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (220 mg, 91%).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][NH2:12])([O-:3])=[O:2].O=[C:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][NH:12][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)([O-:3])=[O:2]
Reactant: NCCc1ccccc1[N+](=O)[O-]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(NCCc2ccccc2[N+](=O)[O-])CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A stirred solution of 2-(2-nitrophenyl)ethanamine (4 g, 24 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (4.8 g, 24 mmol) in MeOH (48 ml) was brought to pH 5 by the addition of acetic acid. NaBH3CN (2.3 g, 36 mmol) was added and the reaction mixture was stirred at RT for 3 hours. The solvent was evaporated and the residue was taken up in EtOAc and sat. aq. Na2CO3. The layers were separated and the organic layer was washed with brine, dried (Na2SO4) and evaporated to dryness. Purification by column chromatography (0% to 7% MeOH in DCM) gave the desired product. LC/MS (10% to 99%): M/Z (M+H)+ (obs)=350; tR=2.22.
Reaction SMILES: O.[OH-].[Na+].[OH:4][C:5]1[CH:6]=[CH:7][C:8]2[C:9]3[C:14]([C:15]4[C:20]=2[C:19]=1[CH:18]=[CH:17][CH:16]=4)=[CH:13][CH:12]=[C:11]([OH:21])[CH:10]=3.Cl.[CH2:23]([N:25]([CH2:30][CH3:31])[CH2:26][CH2:27][CH2:28]Cl)[CH3:24]>C1(C)C=CC=CC=1>[CH2:23]([N:25]([CH2:30][CH3:31])[CH2:26][CH2:27][CH2:28][O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:9]3[C:14]([C:15]4[C:20]=2[C:19]=1[CH:18]=[CH:17][CH:16]=4)=[CH:13][CH:12]=[C:11]([O:21][CH2:28][CH2:27][CH2:26][N:25]([CH2:30][CH3:31])[CH2:23][CH3:24])[CH:10]=3)[CH3:24]
Reactant: CCN(CC)CCCCl
Reactant: Oc1ccc2c(c1)-c1ccc(O)c3cccc-2c13
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: Cc1ccccc1
Product: CCN(CC)CCCOc1ccc2c(c1)-c1ccc(OCCCN(CC)CC)c3cccc-2c13

Procedure:
To 200 ml of water containing 16.0 g (0.4 mole) of sodium hydroxide and 15.7 g (0.067 mole) of 3,9-dihydroxyfluoranthene are added 200 ml of toluene and 27.9 g (0.15 mole) of 3-diethylaminopropyl chloride hydrochloride, and the heterogeneous reaction mixture is stirred at reflux for 24 hours. After cooling, the organic layer is washed with water, dried over magnesium sulfate, and concentrated in vacuo. The residue is crystallized from ether to give 3,9-bis(3-diethylaminopropoxy)-fluoranthene which is converted to the dihydrochloride salt with ethereal HCl and recrystallized from methanolbutanone, M.P. 235°-236.5°C.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.[CH3:11][C@H:12]1[NH:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1>[CH3:11][C@H:12]1[N:17]([C:2]2[CH:7]=[N:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:13]1
Reactant: O=[N+]([O-])c1ccc(Br)cn1
Reactant: C[C@@H]1CN(C(=O)OC(C)(C)C)CCN1
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Product: C[C@@H]1CN(C(=O)OC(C)(C)C)CCN1c1ccc([N+](=O)[O-])nc1
Temperature: 100 °C
Yield: 49.6 %

Procedure:
A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (60 mL), 5-bromo-2-nitropyridine (2.0 g, 10.0 mmol), (R)-tert-butyl 3-methylpiperazine-1-carboxylate (2.0 g, 10.0 mmol), and cesium carbonate (6.5 g, 20 mmol). See FIG. 9. After bubbling nitrogen through the resulting mixture for 30 minutes, XantPhos (579 mg, 1.0 mmol) and tris(di-benzylideneacetone)dipalladium(0) (915 mg, 1.0 mmol) were added, and the reaction mixture was heated at 100° C. for 15 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous layer was separated and extracted with ethyl acetate (150 mL×3). The combined organic layer was washed with brine (50 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with 30:1 DCM/MeOH to afford 109a (1.6 g, 44%) as a yellow solid. MS: [M+H]+ 323. 1H NMR (500 MHz, DMSO) δ 8.21 (d, J=3.5, 1H), 8.18 (d, J=9.0, 1H), 7.43-7.45 (m, 1H), 4.33 (s, 1H), 3.92-3.99 (m, 1H), 3.80 (d, J=12.5, 2H), 3.06-3.23 (m, 3H), 1.43 (s, 9H), 1.09 (d, J=6.5, 3H).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[C:7]([C:10]1[CH:11]=[CH:12][C:13]([O:19][CH2:20][CH3:21])=[C:14]([CH:18]=1)[C:15]([OH:17])=O)(=[O:9])[CH3:8].CN(C)C=O.[NH2:27][C:28]1[C:36]([CH3:37])=[CH:35][CH:34]=[CH:33][C:29]=1[C:30]([NH2:32])=[O:31]>ClCCl.N1C=CC=CC=1>[C:7]([C:10]1[CH:11]=[CH:12][C:13]([O:19][CH2:20][CH3:21])=[C:14]([CH:18]=1)[C:15]([NH:27][C:28]1[C:36]([CH3:37])=[CH:35][CH:34]=[CH:33][C:29]=1[C:30]([NH2:32])=[O:31])=[O:17])(=[O:9])[CH3:8]
Reactant: Cc1cccc(C(N)=O)c1N
Reactant: CCOc1ccc(C(C)=O)cc1C(=O)O
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: CCOc1ccc(C(C)=O)cc1C(=O)Nc1c(C)cccc1C(N)=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 436.6 %

Procedure:
Oxalyl chloride (3.66 g, 0.0288 mol) was added dropwise to a stirred solution of 5-acetyl-2-ethoxy-benzoic acid (3 g, 0.00144 mol) and dimethylformamide (0.1 ml) in dichloromethane (15 ml). The mixture was stirred at room temperature for 3 hours, then the solvent evaporated under vacuum and the residue azeotroped with hexane (3×50 ml). The crude acyl chloride was dissolved in dichloromethane (20 ml) and the solution added dropwise to a stirred solution of 2-amino-3-methylbenzamide (2.16 g, 0.0144 mol) in pyridine (40 ml) at 0° C. The mixture was allowed to warm to room temperature and stirred for a further 18 hours. The solvent was removed by evaporation under vacuum, the residue dissolved in dichloromethane (50 ml) and this solution then washed with saturated aqueous sodium carbonate solution (50 ml), 2N hydrochloric acid (50 ml) and brine (50 ml), then dried (Na2SO4) and evaporated under vacuum. Trituration of the residue with diethyl ether gave the title compound as a white solid (2.14 g, 44%), m.p. 214-216° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]([C:18]1[O:22][C:21]([C:23]2[CH:24]=[C:25]([CH:29]=[C:30]([N:32]([CH3:37])S(C)(=O)=O)[CH:31]=2)[C:26]([OH:28])=[O:27])=[N:20][N:19]=1)([CH3:17])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:38]([S:41](Cl)(=[O:43])=[O:42])([CH3:40])[CH3:39]>>[C:1]([O:5][C:6]([NH:8][C@:9]([C:18]1[O:22][C:21]([C:23]2[CH:24]=[C:25]([CH:29]=[C:30]([N:32]([CH3:37])[S:41]([CH:38]([CH3:40])[CH3:39])(=[O:43])=[O:42])[CH:31]=2)[C:26]([OH:28])=[O:27])=[N:20][N:19]=1)([CH3:17])[CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)S(=O)(=O)Cl
Reactant: CN(c1cc(C(=O)O)cc(-c2nnc(C(C)(Cc3ccccc3)NC(=O)OC(C)(C)C)o2)c1)S(C)(=O)=O
Product: CC(C)S(=O)(=O)N(C)c1cc(C(=O)O)cc(-c2nnc([C@@](C)(Cc3ccccc3)NC(=O)OC(C)(C)C)o2)c1

Procedure:
Prepared using a procedure similar to that employed for the synthesis of Intermediate VI, substituting isopropyl sulfonyl chloride in the place of methanesulfonyl chloride in Step A of the Intermediate III synthesis.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:15]3=[CH:16][C:17]4[O:21][CH2:20][O:19][C:18]=4[CH:22]=[C:14]3[O:13][CH2:12]1)[C:5](=[O:11])[NH:6]2.[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1.CN(C)C1N=CC(B(O)O)=CC=1>>[N:23]1[CH:28]=[C:27]([C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[C:4]2([C:15]4=[CH:16][C:17]5[O:21][CH2:20][O:19][C:18]=5[CH:22]=[C:14]4[O:13][CH2:12]2)[C:5](=[O:11])[NH:6]3)[CH:26]=[N:25][CH:24]=1
Reactant: O=C1Nc2cccc(Br)c2C12COc1cc3c(cc12)OCO3
Reactant: OB(O)c1cncnc1
Agent: CN(C)c1ccc(B(O)O)cn1
Product: O=C1Nc2cccc(-c3cncnc3)c2C12COc1cc3c(cc12)OCO3

Procedure:
Following the procedure as described in EXAMPLE 4, and making non-critical variations using 4′-bromospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one to replace 4′-bromo-1-pentylspiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, and pyrimidin-5-ylboronic acid to replace [6-(dimethylamino)pyridin-3-yl]boronic acid, the title compound was obtained (32%) as a colorless solid: mp 185-187° C.; 1H NMR (300 MHz, DMSO-d6) δ 10.85 (s, 1H), 9.02 (s, 1H), 8.19 (s, 2H), 7.33 (t, 1H), 7.00 (d, 1H), 6.83 (d, 1H), 6.37 (s, 1H), 6.19 (s, 1H), 5.89 (d, 2H); 13C NMR (75 MHz, DMSO-d6) δ 178.7, 157.5, 156.0, 155.6, 148.8, 142.3, 133.1, 132.6, 131.8, 129.5, 124.5, 120.3, 110.9, 103.2, 101.9, 93.3, 79.5, 66.8, 58.5; MS (ES+) m/z 360.4 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[CH:8]=[C:9]([C:16]([OH:18])=O)[C:10](=[CH:14][CH:15]=2)[C:11]([OH:13])=O)=[CH:4][CH:3]=1.[CH2:21]([O:25][C:26](=[O:29])[CH2:27][NH2:28])[CH2:22][CH2:23][CH3:24]>>[CH2:21]([O:25][C:26](=[O:29])[CH2:27][N:28]1[C:16](=[O:18])[C:9]2[C:10](=[CH:14][CH:15]=[C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:20][CH:19]=3)[CH:8]=2)[C:11]1=[O:13])[CH2:22][CH2:23][CH3:24]
Reactant: CCCCOC(=O)CN
Reactant: O=C(O)c1ccc(Oc2ccc(Cl)cc2)cc1C(=O)O
Product: CCCCOC(=O)CN1C(=O)c2ccc(Oc3ccc(Cl)cc3)cc2C1=O
Temperature: 250 °C
Yield: 65.8 %

Procedure:
A mixture of 500 mg 4-(4-Chloro-phenoxy)-phthalic acid and glycine n-butyl ester (286 mg) was heated at 250° C. for 5 min. The reaction mixture was purified by chromatography with dichloromethane as eluent to give 436 mg the title compound. 1H NMR (200 MHz, DMSO) δ 7.48 (d, J=8.6 Hz, 1H), 7.59 (d, J=9.0 Hz, 2H), 7.46 (m, 2H), 7.29 (d, J=9.0 Hz, 2H), 4.46 (s, 2H), 4.16 (t, J=6.2 Hz, 2H), 1.61 (m, 2H), 1.38 (m, 2H), 0.92 (t, J=7.0 Hz, 3H).
Reaction SMILES: [SiH:1]([Cl:4])([Cl:3])[Cl:2].[CH2:5]([Cl:9])[C:6](=[CH2:8])[CH3:7].[CH3:10][SiH:11]([Cl:13])[Cl:12]>>[CH3:10][Si:11]([CH2:8][CH:6]([CH2:5][Cl:9])[CH3:7])([Cl:13])[Cl:12].[Si:1]([CH2:7][CH:6]([CH2:5][Cl:9])[CH3:8])([Cl:4])([Cl:3])[Cl:2]
Reactant: Cl[SiH](Cl)Cl
Reactant: C[SiH](Cl)Cl
Reactant: C=C(C)CCl
Product: CC(CCl)C[Si](C)(Cl)Cl
Product: CC(CCl)C[Si](Cl)(Cl)Cl
Yield: 68.8 %
Yield: 21.5 %

Procedure:
In a 100 ml apparatus, there as combined 13.6 g (0.1 mol) of Cl3SiH, 9.1 g (0.1 mol) of methallyl chloride, and 11.5 g (0.1 mol) of MeSiHCl2, followed by 0.05 ml Pt catalyst solution at 21° C. Gentle heating caused an exothermic reaction to 52° C. in 22 min. The complete reaction was vacuum distilled, yielding 14.14 g (68.8%) of MeSiCl2CH2CHMeCH2Cl and 4.86 g (21.5%) of Cl3SiCH2CHMeCH2Cl. This example indicates that at the equimolar level, neither Cl3SiH nor MeSiHCl2 is an effective promoter for reactions of the other with methallyl chloride.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([NH:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:4][CH:3]=1.[N+](C1C=CC=CC=1)([O-])=O.[Br:36]Br.S([O-])(O)=O.[Na+]>O>[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([NH:18][C:19](=[O:26])[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[CH:4][C:3]=1[Br:36]
Reactant: BrBr
Reactant: Nc1ccc(NC(=O)c2ccccc2)c2c1C(=O)c1ccccc1C2=O
Agent: O=S([O-])O
Agent: [Na+]
Solvent: O
Solvent: O=[N+]([O-])c1ccccc1
Product: Nc1c(Br)cc(NC(=O)c2ccccc2)c2c1C(=O)c1ccccc1C2=O
Temperature: 20 °C
Yield: 86.5 %

Procedure:
With stirring, 85.5 parts of 1-amino-4-benzoylaminoanthraquinone are suspended in 200 parts of nitrobenzene. The suspension is diluted with 100 parts of water and then a solution of 50.4 parts of bromine in 60 parts of nitrobenzene is added in the course of 1 hour at 30°-35° C. The reaction is brought to completion by stirring for 3 hours at 50°-55° C. The mixture is cooled to 30°-35° C. and, after addition of 65 parts of a 40% sodium hydrogen sulfite solution, stirred for 1/2 hour and cooled to 20° C. Finally, the reaction product is collected by suction, washed with 60 parts of nitrobenzene as well as with ethanol and hot water, and dried, affording 91 parts (86.5% of theory) of 1-amino-2-bromo-4-benzoylaminoanthraquinone with a melting point of 241° C.-243° C. Br: calculated 18.97%, found 18.5%.
Reaction SMILES: [CH3:1][C:2]([C:4]1[C:9]([O:10][CH3:11])=[CH:8][CH:7]=[CH:6][C:5]=1[O:12][CH3:13])=[O:3].[C:14]([O:19][CH2:20]C)(=[O:18])[C:15]([O-])=[O:16].C[O-].[Na+:24].[Na].C(OC(C)C)(C)C>CO>[Na+:24].[CH3:13][O:12][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([O:10][CH3:11])[C:4]=1[C:2]([O-:3])=[CH:1][C:15](=[O:16])[C:14]([O:19][CH3:20])=[O:18]
Reactant: COc1cccc(OC)c1C(C)=O
Reactant: CCOC(=O)C(=O)[O-]
Agent: C[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CO
Solvent: CC(C)OC(C)C
Product: COC(=O)C(=O)C=C([O-])c1c(OC)cccc1OC
Reaction time: 8 h

Procedure:
A solution of 100 g of 2,6-dimethoxyacetophenone and 7.5 ml of ethyl oxalate in 520 ml of anhydrous MeOH is added slowly to a solution of sodium methylate prepared from 12.7 g of sodium and 285 ml of anhydrous MeOH. The reaction mixture is heated to reflux for 7 hours and left overnight at RT. It is poured into 2 liters of isopropyl ether and left stirring for 15 minutes. The expected product is obtained by filtration, washing with isopropyl ether and drying under vacuum, m=120 g, m.p.=178° C.
Reaction SMILES: C[O:2][C:3]([C:5]1[NH:6][C:7](=[O:10])[S:8][CH:9]=1)=O.[OH-].[NH4+:12]>>[NH2:12][C:3]([C:5]1[NH:6][C:7](=[O:10])[S:8][CH:9]=1)=[O:2]
Reactant: [NH4+]
Reactant: COC(=O)c1csc(=O)[nH]1
Agent: [OH-]
Product: NC(=O)c1csc(=O)[nH]1
Reaction time: 24 h

Procedure:
48 g of 4-methoxycarbonyl-4-thiazoline-2-one were added to 600 ml of concentrated aqueous ammonium hydroxide and the mixture was stirred for 24 hours. The mixture was acidified and filtered to obtain 30 g of 4-aminocarbonyl-4-thiazoline-2-one in the form of white crystals melting at 261°C.