Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9]C(=O)[C:7]2=[O:12].[OH:13]O.Cl>[OH-].[Na+]>[NH2:9][C:10]1[C:2]([F:1])=[CH:3][CH:4]=[CH:5][C:6]=1[C:7]([OH:12])=[O:13]
Reactant: O=C1Nc2c(F)cccc2C1=O
Reactant: OO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Nc1c(F)cccc1C(=O)O
Temperature: 70 °C
Reaction time: 1 h
Yield: 59 %

Procedure:
A solution of 7-fluoro-1H-indol-2,3-dione (13.0 g, 78.7 mmol) in 10N sodium hydroxide (125 mL) was heated and stirred at 70° C. for 1 hour. 30% Hydrogen peroxide (25 mL) was added dropwise over 20 minutes at the same temperature, and the mixture was heated and stirred at the same temperature further for 1 hour. The solution was ice cooled, and conc. hydrochloric acid was added to the solution carefully until the pH of the solution became 4. Organic matter was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The crystals thus obtained were collected by filtration to give the title compound (7.15 g, 59% yield).
Reaction SMILES: [C:1]1([C@@H:7]2[CH2:9][C@H:8]2[C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:14][O:15][NH:16][CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH3:14][O:15][N:16]([CH3:17])[C:10]([C@@H:8]1[CH2:9][C@H:7]1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:12]
Reactant: O=C(O)[C@@H]1C[C@H]1c1ccccc1
Reactant: CNOC
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CON(C)C(=O)[C@@H]1C[C@H]1c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 42 %

Procedure:
To a stirred solution of 35 (117.5 g, 724.48 mmol, 1.00 equiv) in DMF (1.2 L) under N2 was added methoxy(methyl)amine hydrochloride (82.3 g, 844.10 mmol, 1.17 equiv), HATU (329 g, 775.58 mmol, 1.07 equiv), and DIPEA (117.5 mL). The reaction mixture was stirred under N2 at 25° C. overnight and then diluted with water (700 mL). The organic phase was extracted with EtOAc (3×1 L), and the combined organic layers were washed with water (3×1 L) and brine (1×1 L), dried (Na2SO4), filtered and concentrated in vacuo. The residue purified by SiO2 chromatography and eluted with EtOAc/petroleum ether (10 to 50% EtOAc) to afford 62.5 g (42%) of trans-N-methoxy-N-methyl-2-phenylcyclopropane-1-carboxamide (37) as a light yellow oil.
Reaction SMILES: [C:1]1([N:7]2[CH2:13][CH2:12][CH2:11][CH2:10][NH:9][S:8]2(=[O:15])=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Br:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25]Br)=[C:21]([F:27])[CH:20]=1>CN(C=O)C.CCOC(C)=O.O>[Br:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][N:9]2[CH2:10][CH2:11][CH2:12][CH2:13][N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[S:8]2(=[O:15])=[O:14])=[C:21]([F:27])[CH:20]=1
Reactant: Fc1cc(Br)ccc1CBr
Reactant: O=S1(=O)NCCCCN1c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=S1(=O)N(Cc2ccc(Br)cc2F)CCCCN1c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 60 %

Procedure:
A solution of 2-phenyl-1λ6,2,7-thiadiazepane-1,1-dione (500 mg, 2.21 mmol) and NaH (214 mg, 6.63 mmol) in DMF (15 mL) was stirred at 0° C. for 10 minutes. To the solution was added a solution of 4-bromo-1-(bromomethyl)-2-fluorobenzene (881 mg, 3.32 mmol) in DMF (5 mL) and stirred at room temperature for 3 hours. The reaction mixture was diluted with EtOAc and water, extracted with ethyl acetate, dried over Na2SO4, filtered, and concentrated under reduced pressure to afford 2-[(4-bromo-2-fluorophenyl)methyl]-7-phenyl-1λ6,2,7-thiadiazepane-1,1-dione as a yellow oil (548 mg, 60%). LCMS (ESI): m/z=413.0 [M+H]+.
Reaction SMILES: C([SiH](CC)CC)C.[CH2:8]([C@H:15]1[CH2:19][O:18][C:17](=[O:20])[N:16]1[C:21](=[O:42])[C@@H:22]([O:32][C:33]1[CH:38]=[CH:37][C:36]([CH:39]([CH3:41])[CH3:40])=[CH:35][CH:34]=1)[C@H:23](O)[C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>FC(F)(F)C(O)=O>[CH2:8]([C@H:15]1[CH2:19][O:18][C:17](=[O:20])[N:16]1[C:21](=[O:42])[C@@H:22]([O:32][C:33]1[CH:38]=[CH:37][C:36]([CH:39]([CH3:40])[CH3:41])=[CH:35][CH:34]=1)[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(C)c1ccc(O[C@H](C(=O)N2C(=O)OC[C@@H]2Cc2ccccc2)[C@H](O)c2ccc(O)cc2)cc1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CC(C)c1ccc(O[C@@H](Cc2ccc(O)cc2)C(=O)N2C(=O)OC[C@@H]2Cc2ccccc2)cc1
Reaction time: 18 h
Yield: 61.5 %

Procedure:
Triethylsilane (30.2 ml) was added to a solution of (S)-4-benzyl-3-[(2S,3R)-3-hydroxy-3-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)propionyl]oxazolidine-2-one (18.0 g), which is the product of Reference example 29(c), in trifluoroacetic acid (150 ml) at ambient temperature. The mixture was stirred for 18 hours. The reaction mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water and the layers were separated. The ethyl acetate layer was washed with saturated aqueous sodium hydrogencarbonate solution, aqueous hydrogen chloride solution (1N) and saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified via chromatography on a silica gel column using hexane/ethyl acetate=3/1 as the eluant to afford the desired compound (10.7 g) as colorless crystals.
Reaction SMILES: Br[C:2](=[CH2:22])[CH2:3][C:4]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[CH:23]1([B-](F)(F)F)[CH2:25][CH2:24]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CCOC(C)=O.O.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]>[CH:23]1([C:2](=[CH2:22])[CH2:3][C:4]2([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]2)[CH2:25][CH2:24]1
Reactant: C=C(Br)CC1(C(=O)OCC)CCN(C(=O)OC(C)(C)C)CC1
Reactant: F[B-](F)(F)C1CC1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: C=C(CC1(C(=O)OCC)CCN(C(=O)OC(C)(C)C)CC1)C1CC1
Temperature: 80 °C

Procedure:
1-tert-butyl 4-ethyl 4-(2-bromoallyl)piperidine-1,4-dicarboxylate (1.0 g, 2.66 mmol), potassium cyclopropyltrifluoroborate (0.413 g, 2.79 mmol), cesium carbonate (2.60 g, 7.97 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.058 g, 0.080 mmol) were taken up in toluene (14 mL) and water (1.39 mL) in a microwave vial, degassed and heated at 80° C. overnight. The reaction mixture was cooled and LC/MS was taken which showed almost completion of reaction. The reaction mixture was diluted with EtOAc and water. Aqueous layer was extracted with EtOAc (2×), the combined organic layers were dried over anhydrous MgSO4, filtered, concentrated, and purified by silica gel column chromatography (RediSep Gold, 80 g) using (0-30) % EtOAc/Hexanes as mobile phase to afford the title compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:16]([C:17]4[CH:18]=[N:19][N:20]([CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=5)[CH:21]=4)=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1[N:30]1[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:16]([C:17]4[CH:18]=[N:19][N:20]([CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=5)[CH:21]=4)=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1[N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(-c3cnc4[nH]cc(-c5cnn(Cc6cccc(F)c6)c5)c4c3)cc2F)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Fc1cccc(Cn2cc(-c3c[nH]c4ncc(-c5ccc(N6CCNCC6)c(F)c5)cc34)cn2)c1
Yield: 18.2 %

Procedure:
Using similar reaction conditions as described in step-ii of example-7, tert-butyl 4-(2-fluoro-4-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazine-1-carboxylate (80 mg, 0.140 mmol) was deprotected in TFA/DCM (5/5 ml) to afford 12 mg (93% yield) of the titled compound. 1H NMR (CD3OD, 300 MHz): δ 8.54 (s, 2H), 8.262-8.260 (d, 1H), 7.975-7.973 (d, 1H), 7.74 (s, 1H), 7.59-7.52 (m, 2H), 7.38-7.00 (m, 5H), 5.44 (s, 2H), 3.42-3.40 (m, 8H). MS: m/z=471.2 (M+1), HPLC: 97.06% in method B.
Reaction SMILES: [F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]([CH2:12][C:13]1[CH:18]=[C:17]([N+:19]([O-])=O)[CH:16]=[CH:15][C:14]=1[C:22]1[CH:27]=[C:26]([CH:28]([CH3:30])[CH3:29])[CH:25]=[CH:24][C:23]=1[O:31][CH3:32])[C:8](=[O:11])[O:9][CH3:10].[H][H]>CO.[Pd]>[NH2:19][C:17]1[CH:16]=[CH:15][C:14]([C:22]2[CH:27]=[C:26]([CH:28]([CH3:30])[CH3:29])[CH:25]=[CH:24][C:23]=2[O:31][CH3:32])=[C:13]([CH2:12][N:7]([CH2:6][C:5]2[CH:33]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:35]=[C:3]([C:2]([F:1])([F:40])[F:41])[CH:4]=2)[C:8](=[O:11])[O:9][CH3:10])[CH:18]=1
Reactant: [H][H]
Reactant: COC(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Cc1cc([N+](=O)[O-])ccc1-c1cc(C(C)C)ccc1OC
Agent: [Pd]
Solvent: CO
Product: COC(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Cc1cc(N)ccc1-c1cc(C(C)C)ccc1OC

Procedure:
A solution of the methyl [3,5-bis(trifluoromethyl)benzyl][(5′-isopropyl-2′-methoxy-4-nitrobiphenyl-2-yl)methyl]carbamate from Example 8 (0.31 g, 0.53 mmol) in MeOH (10 ml) was charged with a catalytic amount Pd/C and hydrogen at 40 psi for 1 h. The mixture was filtered through Celite and the filtrate was concentrated. The title compound was obtained by flash column chromatography using 3:7 EtOAc/hexane as the eluant. 1H NMR (CDCl3, 500 MHz) δ 7.72 (m, 1H), 7.50 (s, 1H), 7.30 (s, 1H), 7.16 (m, 1H), 7.03 (d, J=8.0 Hz, 1H), 6.94 (s, 1H), 6.82 (m, 1H), 6.69 (dd, J=8.5, 2.5 Hz, 1H), 6.58 (m, 1H), 4.18-4.30 (m, 4H), 3.75 (s, 3H), 3.65 (s, 3H), 2.83 (m, 1H), 1.20 (s, 6H). LC-MS (M+1): 555.3 (3.58 min).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[C:5](Cl)(=[O:7])[CH3:6].[Br:9][C:10]1[C:11]([CH3:21])=[CH:12][C:13]2[O:17][CH2:16][C:15]([CH3:19])([CH3:18])[C:14]=2[CH:20]=1.O>ClCCl>[Br:9][C:10]1[C:11]([CH3:21])=[C:12]([C:5](=[O:7])[CH3:6])[C:13]2[O:17][CH2:16][C:15]([CH3:18])([CH3:19])[C:14]=2[CH:20]=1
Reactant: CC(=O)Cl
Reactant: Cc1cc2c(cc1Br)C(C)(C)CO2
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Product: CC(=O)c1c(C)c(Br)cc2c1OCC2(C)C
Temperature: 25 °C
Yield: 61.6 %

Procedure:
A stirred, cooled (ice-bath) suspension of aluminum chloride (6.85 g, 51.4 mmol) in 50 mL of anhydrous dichloromethane was treated with acetyl chloride (3.7 mL, 51.4 mmol) under argon. A solution of 5-bromo-3,3,3-trimethyl-2,3-dihydro-benzofuran (Compound 47, 5.2 5 g, 25.7 mmol)in 10 mL of anhydrous dichloromethane was cannulated into the clear solution, and the resulting deep red solution was allowed to warm to ambient temperature over 1 hour. The reaction mixture was poured onto iced water and extracted with dichloromethane. The combined organic extract was dried over anhydrous sodium sulfate, filtered and evaporated to a dirty white solid. Flash column chromatography on silica gel using 6% ethyl acetate in hexane as the eluent afforded the title compound (4.5 g, 61.6%). 1H NMR (300 MHz, CDCl3): δ 7.30 (s, 1H), 4.28 (s, 2H), 2.56 (s, 3H), 2.34 (s, 3H), 1.33 (s, 6H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][N:5]1[C:9](=[O:10])[N:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[C:7](Br)=[N:6]1.[OH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O>>[CH3:1][O:2][C:3](=[O:20])[CH2:4][N:5]1[C:9](=[O:10])[N:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[C:7]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[OH:21])=[N:6]1
Reactant: COC(=O)Cn1nc(Br)n(Cc2cccc(F)c2)c1=O
Reactant: OB(O)c1ccccc1O
Product: COC(=O)Cn1nc(-c2ccccc2O)n(Cc2cccc(F)c2)c1=O

Procedure:
By the method described for Example 147A, starting from 250 mg (0.73 mmol) of the compound from Example 146A and 138 mg of (1.02 mmol) 2-hydroxyphenylboronic acid, 22 mg (8% of theory) of the title compound and 222 mg (85% of theory) of the corresponding acid formed by hydrolysis (see also Example 150A) are obtained.
Reaction SMILES: Cl.[C:2]([O:5][C@H:6]1[C@H:11]([NH2:12])[C@@H:10]([O:13][C:14](=[O:16])[CH3:15])[C@H:9]([O:17][C:18](=[O:20])[CH3:19])[C@@H:8]([CH2:21][O:22][C:23](=[O:25])[CH3:24])[O:7]1)(=[O:4])[CH3:3].Cl.CN(C)CCCN=C=NCC.[C:38]1([CH2:44][C:45](O)=[O:46])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:2]([O:5][C@H:6]1[C@H:11]([NH:12][C:45](=[O:46])[CH2:44][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@@H:10]([O:13][C:14](=[O:16])[CH3:15])[C@H:9]([O:17][C:18](=[O:20])[CH3:19])[C@@H:8]([CH2:21][O:22][C:23](=[O:25])[CH3:24])[O:7]1)(=[O:4])[CH3:3]
Reactant: O=C(O)Cc1ccccc1
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](N)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](NC(=O)Cc2ccccc2)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reaction time: 12 h
Yield: 68.6 %

Procedure:
To a suspension of (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-amino-tetrahydro-2H-pyran-2,4,5-triyl triacetate hydrochloride (0.500 g, 1.31 mmol) in CH2Cl2 (20 mL) was added 4-(dimethylamino)pyridine (0.478 g, 3.91 mmol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.300 g, 1.57 mmol) and 2-phenylacetic acid (0.2132 g, 1.57 mmol). The reaction was stirred for 12 h. Additional CH2Cl2 (80 mL) was added and the organic layer was washed once with saturated aqueous NaHCO3 (10 mL). The organic layer was then dried (MgSO4) and concentrated in vacuo. Flash chromatography of the crude material on silica gel (3:2 EtOAc:hexanes) followed by crystallization (EtOAc/hexanes) afforded (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(2-phenylacetamido)-tetrahydro-2H-pyran-2,4,5-triyl triacetate as a white solid (0.418 g, 69% yield).
Reaction SMILES: [Cl:1]Cl.[Cl:3][Si:4]([Cl:11])([Cl:10])[CH2:5][Si:6]([Cl:9])([CH3:8])[CH3:7].N(C(C)(C)C#N)=NC(C)(C)C#N>C(Cl)(Cl)(Cl)Cl>[Cl:3][Si:4]([Cl:11])([Cl:10])[CH2:5][Si:6]([Cl:9])([CH3:8])[CH2:7][Cl:1]
Reactant: ClCl
Reactant: C[Si](C)(Cl)C[Si](Cl)(Cl)Cl
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: C[Si](Cl)(CCl)C[Si](Cl)(Cl)Cl
Reaction time: 5 h

Procedure:
A stirrer was added to a 250 ml, round bottomed flask, which was equipped with a bubbling column linked to a dry ice/aceton condenser and a chlorine gas cylinder. To the flask were added 100 g (0.41 mole) of 1,1,1,3-tetrachloro-3-methyl-1,3-disilabutane and 1 g of a reaction initiator, azobisisobutyronitrile, using carbon tetrachloride as a solvent. The obtained mixture was photoreacted for 5 hrs using a sun lamp, while bubbling chlorine gas and refluxing carbon tetrachloride. After confirming the degree of the reaction process by gas chromatography, the reaction mixture was distilled under vacuum to obtain 38 g of 1,1,1,3,4-pentachloro-3-methyl-1,3-disilabutane.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[C:6]([CH2:11][CH2:12][OH:13])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:33]([O:37][C:38](=[O:57])[CH2:39][CH:40]([NH:45][S:46]([C:49]1[CH:54]=[CH:53][C:52]([NH2:55])=[CH:51][C:50]=1O)(=[O:48])=[O:47])[C:41]([NH:43][CH3:44])=[O:42])([CH3:36])([CH3:35])[CH3:34].N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[C:33]([O:37][C:38](=[O:57])[CH2:39][CH:40]([NH:45][S:46]([C:49]1[CH:54]=[CH:53][C:52]([NH2:55])=[CH:51][C:50]=1[O:13][CH2:12][CH2:11][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:5]=1[CH:4]=[CH:3][CH:2]=[N:1]2)(=[O:48])=[O:47])[C:41]([NH:43][CH3:44])=[O:42])([CH3:36])([CH3:34])[CH3:35]
Reactant: CNC(=O)C(CC(=O)OC(C)(C)C)NS(=O)(=O)c1ccc(N)cc1O
Reactant: OCCc1cccc2ncccc12
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CNC(=O)C(CC(=O)OC(C)(C)C)NS(=O)(=O)c1ccc(N)cc1OCCc1cccc2ncccc12
Reaction time: 18 h

Procedure:
A mixture of 0.167 g (0.972 mmol) 2-quinolin-5-yl-ethanol, 0.48 g (1.94 mmol) triphenyl phosphine, and 0.392 g (0.972 mmol) 3-(4-amino-2-hydroxy-benzenesulfonylamino)-N-methyl-succinamic acid tert-butyl ester was stirred in 25 mL THF at room temperature under a nitrogen atmosphere. 0.31 mL (1.94 mmol) diethyl azodicarboxylate was added dropwise and the mixture stirred 18 h. TLC anaylsis indicated complete reaction. The solvent was evaporated under reduced pressure and the residue purified on silica eluting with 1:1 hexanes:EtOAc to EtOAc yielding 0.23 g (43%) of 3-(4-amino-2-(2-quinolin-5-yl-ethoxy)-benzenesulfonylamino)-N-methyl-succinamic acid tert-butyl ester as a colorless foam. MS (APCI) m/z 559 (M+1).
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:8]1[CH:9]=[N:10][C:11]([Cl:14])=[N:12][CH:13]=1.[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O>O1CCOCC1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:14][C:11]1[N:10]=[CH:9][C:8]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[F:15])=[CH:13][N:12]=1
Reactant: Clc1ncc(Br)cn1
Reactant: OB(O)c1ccccc1F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1COCCO1
Product: Fc1ccccc1-c1cnc(Cl)nc1
Temperature: 90 °C
Reaction time: 3 h

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (2.06 g, 1.79 mmol, 0.1 eq) and caesium carbonate (17.4 g, 53.69 mmol, 2.0 eq) were added under an argon atmosphere to a stirred solution of 5-bromo-2-chloropyrimidine (2.5 g, 17.86 mmol, 1 eq) and (2-fluorophenyl)boronic acid (3.45 g, 17.86 mmol, 1.0 eq) in 1,4-dioxane/water (30 mL, 4:1) at room temperature. The mixture was heated to 90° C., stirred for 3 h and then cooled to room temperature. The mixture was diluted with ethyl acetate (10 mL), washed with water, and dried over sodium sulfate. The solvents were removed in vacuo and the residue was purified by column chromatography [silica gel 100-200 mesh, ethyl acetate/petrolether 1:19]. Yield: 2.0 g (53% of theory)
Reaction SMILES: OS(O)(=O)=O.[N+:6]([O-:9])(O)=[O:7].[CH3:10][N:11]1[C:16]([CH3:17])=[CH:15][C:14](=[O:18])[N:13]([CH3:19])[C:12]1=[O:20]>>[CH3:10][N:11]1[C:16]([CH3:17])=[C:15]([N+:6]([O-:9])=[O:7])[C:14](=[O:18])[N:13]([CH3:19])[C:12]1=[O:20]
Reactant: Cc1cc(=O)n(C)c(=O)n1C
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: Cc1c([N+](=O)[O-])c(=O)n(C)c(=O)n1C
Temperature: 2.5 °C
Reaction time: 2 h

Procedure:
A mixture of concentrated H2SO4 (7.0 mL) and fuming HNO3 (7.0 mL) was cooled to 0-5° C. and 1,3,6-trimethylpyrimidine-2,4(1H,3H)-dione (3.5 g, 22.702 mmol) was gradually added to the reaction mixture. After stirring for 2 h. at the same temperature the reaction mixture was partitioned between ethyl acetate (200 mL) and water (100 mL). The organic layer was washed with brine (2×50 mL), dried (Na2SO4) and evaporated under reduced pressure. Crude product obtained was purified by column chromatography to give 1.30 g of the product as yellow solid; 1H NMR (δ ppm, 300 MHz, DMSO-d6) 2.38 (s, 3H), 3.20 (s, 3H), 3.40 (s, 3H); APCI-MS (m/z) 198.30 (M−H).
Reaction SMILES: [CH3:1][CH:2]([OH:40])[CH2:3][C:4]1[C:24]2=[C:25]3[C:7]([C:8]([CH:10]=[C:11]([O:35][CH3:36])[C:12]3=[C:13]3[C:23]4[C:18](=[C:19]([OH:32])[C:20]([O:30][CH3:31])=[C:21]([CH2:26][CH:27](O)[CH3:28])[C:22]=42)[C:16](=[O:17])[CH:15]=[C:14]3[O:33][CH3:34])=[O:9])=[C:6]([OH:37])[C:5]=1[O:38][CH3:39].ClCCl>CS(C)=O.C(OC(=O)C)(=O)C>[CH3:28][C:27]1[CH2:26][C:21]2[C:22]3[C:23]4[C:18]([C:19]([C:20]=2[O:30][CH3:31])=[O:32])=[C:16]([OH:17])[CH:15]=[C:14]([O:33][CH3:34])[C:13]=4[C:12]2[C:25]4[C:24]=3[C:4](=[C:5]([O:38][CH3:39])[C:6]([C:7]=4[C:8]([OH:9])=[CH:10][C:11]=2[O:35][CH3:36])=[O:37])[C:3]=1[C:2]([CH3:1])=[O:40]
Reactant: COc1c(O)c2c(=O)cc(OC)c3c4c(OC)cc(=O)c5c(O)c(OC)c(CC(C)O)c(c(c1CC(C)O)c23)c54
Solvent: CC(=O)OC(C)=O
Solvent: CS(C)=O
Solvent: ClCCl
Product: COc1c2c3c4c(c(OC)c(=O)c5c(O)cc(OC)c(c6c(OC)cc(O)c(c1=O)c63)c54)C(C(C)=O)=C(C)C2
Yield: 26 %

Procedure:
A solution of Phleichrome (100 mg) in DMSO (2 mL) and acetic anhydride (1 mL) was heated at 40° C. for 24 h. The reaction mixture was diluted by dichloromethane (15 mL), washed with water and evaporated. The residue was chromatographed on two silica gel columns (1-5% MeOH-dichloromethane) to provide Hypocrellin B (25 mg, ˜25%). Thin-layer chromatography results and 1H-NMR were identical to that obtained from naturally occurring and extracted Hypocrellin B from H. bambusae, and as obtained by the two-step chemical conversion (Scheme 2).
Reaction SMILES: [CH:1]1[C:6]2[C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[O:9][C:5]=2[CH:4]=[C:3]([C:14]([O:16]C)=[O:15])[N:2]=1.[OH-].[Na+]>CO.O>[CH:1]1[C:6]2[C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[O:9][C:5]=2[CH:4]=[C:3]([C:14]([OH:16])=[O:15])[N:2]=1
Reactant: COC(=O)c1cc2oc3ccccc3c2cn1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)c1cc2oc3ccccc3c2cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.1 %

Procedure:
Methyl benzofuro[3,2-c]pyridine-3-carboxylate (2.02 g, 8.89 mmol) is dissolved in MeOH (50 ml) and water (10 ml). 2M NaOH (5.3 ml, 10.67 mmol) is added dropwise, and the reaction stirred overnight at rt. When the reaction is complete by TLC, the volatiles are removed in vacuo. The solid residue is suspended in water (40 ml) and the pH is adjusted to 3 with concentrated HCl. The white slurry is filtered, and the cake is dried first in a stream of air and then in a vacuum oven overnight, affording 1.84 g (97%) of benzofuro[3,2-c]pyridine-3-carboxylic acid as a pale yellow solid. 1H NMR (DMSO-d6) δ 7.56 (t, J=8 Hz), 7.68 (t, J=7 Hz), 7.877 (d, J=8 Hz), 8.38 (m), 9.51 ppm.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:7]([O:10]C)=[CH:6][C:4]=1[NH2:5].C[O:13][C:14]1[CH:22]=[CH:21][C:17](C(Cl)=O)=[CH:16][CH:15]=1>>[OH:13][C:14]1[CH:22]=[CH:21][C:17]([C:1]2[O:2][C:3]3[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][C:4]=3[N:5]=2)=[CH:16][CH:15]=1
Reactant: COc1ccc(OC)c(N)c1
Reactant: COc1ccc(C(=O)Cl)cc1
Product: Oc1ccc(-c2nc3cc(O)ccc3o2)cc1

Procedure:
The title compound was prepared in substantially the same manner as described in Example 1, from 2,5-dimethoxyaniline, and 4-methoxybenzoyl chloride and was obtained as a light yellow solid, m.p. 264-267° C.; MS male 228 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]#[N:8])[N:6]=1.[Br:9]Br>CC(O)=O>[NH2:1][C:2]1[S:3][C:4]([Br:9])=[C:5]([C:7]#[N:8])[N:6]=1
Reactant: N#Cc1csc(N)n1
Reactant: BrBr
Solvent: CC(=O)O
Product: N#Cc1nc(N)sc1Br
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 52.6 %

Procedure:
2-Aminothiazole-4-carbonitrile (1.40 g, 11.18 mmol) was dissolved in 20 mL AcOH in a 150 mL round bottom flask. Br2 (1.78 g, 11.18 mmol) was added to the reaction in a dropwise manner. After stirring at room temperature for 10 minutes, AcOH was removed under vacuum. Saturated sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine and dried over sodium sulfate. 2-amino-5-bromothiazole-4-carbonitrile (1.20 g, yield: 53%) was obtained. LCMS (API-ES) m/z (%): 205.9 (100%, M++2H).
Reaction SMILES: [C:1]1([P:7]([CH2:15][CH:16]=O)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[NH2:19][OH:20].[OH-].[Na+].Cl>C(O)C.O>[C:1]1([P:7]([CH2:15]/[CH:16]=[N:19]\[OH:20])([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NO
Reactant: O=CCP(=O)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=P(C/C=N\O)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98 %

Procedure:
To a suspension of (diphenyl-phosphinoyl)-acetaldehyde example 1d (2.4 g, 9.0 mmol) and hydroxylamine hydrochloride (0.68 g, 10.0 mmol) in ethanol (50 mL) and water (100 mL) was added at 0° C. an aqueous solution of sodium hydroxide (50%, 5 mL) added dropwise within a 10 min period. After stirring at room temperature overnight, the resulting mixture was acidified with HCl (4 N). The mixture was then extracted with dichloromethane and the combined organic layers were then washed with water and brine and then dried over sodium sulfate, filtered and evaporated to afford the title compound (3.75 g, 98%) which was obtained as a light yellow solid. MS m/e (EI): 260.0 [M].