Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl.CCOC(C)=O>[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:12])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)O
Reactant: Nc1ccccc1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)Nc1ccccc1
Reaction time: 8 h

Procedure:
To a mixture of N-Boc-L-proline (1.0 g, 4.65 mmol), aniline (0.433 g. 4.65 mmol), and HOBT (0.753 g, 5.58 mmol) in 10 mL of CH2Cl2 was added EDC (1.07 g, 5.58 mmol) and the solution was stirred overnight. To the solution was added 70 mL of EtOAc and washed with 50 mL 3N HCl, 50 mL water, 50 mL NaHCO3 (sat.), 50 mL 10% K2CO3, and 50 mL brine. The organic layer was then dried over MgSO4, filtered and concentrated under reduced pressure to give a white solid (1.2 g. 89%. ES (+) MS m/e=291 (M+H).
Reaction SMILES: P(=[S:5])([O-])([O-])[O-].[Na+].[Na+].[Na+].Cl.[C:10]([O:13][C@@H:14]1[CH2:18][CH2:17][N:16]([C:19](=[NH:22])[CH2:20][Cl:21])[CH2:15]1)(=[O:12])[NH2:11].Cl>O>[ClH:21].[C:10]([O:13][C@@H:14]1[CH2:18][CH2:17][N:16]([C:19](=[NH:22])[CH2:20][SH:5])[CH2:15]1)(=[O:12])[NH2:11]
Reactant: N=C(CCl)N1CC[C@@H](OC(N)=O)C1
Reactant: [O-]P([O-])([O-])=S
Agent: Cl
Agent: [Na+]
Solvent: O
Product: N=C(CS)N1CC[C@@H](OC(N)=O)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 104.3 %

Procedure:
0.945 g of trisodium phosphorothioate were added to a solution of 1.21 g of 2-[(3R)-3-carbamoyloxypyrrolidin-1-yl]-2-iminoethylchloride hydrochloride in 8 ml of water, kept cooled in ice-water, and the mixture was stirred for about 3 hours at room temperature. After adding 6 ml of 1N hydrochloric acid, the mixture was heated to 50° C. for 30 minutes, and the solvent was then distilled off under reduced pressure. The concentrate was mixed with 8 ml of methanol, insolubles were filtered off, and the filtrate was concentrated under reduced pressure. The concentrate was crystallized by adding ether, and the crystals were collected by filtration and washed with ether, giving 1.25 g of 2-[(3R)-3-carbamoyloxypyrrolidin-1-yl]-2-iminoethylmercaptan hydrochloride.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:16][C:17]1[N:18]=[C:19]([CH3:22])[S:20][CH:21]=1)[C:11]1[CH2:10][CH2:9][C@@H:8]([NH:23][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])[CH2:7][C:6]2=1)=O.Cl.[CH3:30][O:31][NH2:32]>N1C=CC=CC=1.O.Cl.CCOC(C)=O>[CH3:30][O:31][N:32]=[CH:1][C:3]1[CH:4]=[C:5]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:16][C:17]1[N:18]=[C:19]([CH3:22])[S:20][CH:21]=1)[C:11]1[CH2:10][CH2:9][C@@H:8]([NH:23][C:24](=[O:28])[CH:25]([CH3:26])[CH3:27])[CH2:7][C:6]2=1
Reactant: CON
Reactant: Cc1nc(Cn2c3c(c4cc(C=O)ccc42)C[C@H](NC(=O)C(C)C)CC3)cs1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Solvent: O
Product: CON=Cc1ccc2c(c1)c1c(n2Cc2csc(C)n2)CC[C@@H](NC(=O)C(C)C)C1
Temperature: 25 °C
Reaction time: 18 h
Yield: 61.6 %

Procedure:
Dissolve (R)-N-[6-formyl-9-(2-methyl-thiazol-4-ylmethyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide (Example 211) (53 mg, 0.13 mmol) and methoxyamine HCl (22 mg, 0.27 mmol) in pyridine (1 mL). Stir the reaction mixture for 18 h at 25° C. Dilute the reaction mixture with water (2 mL), 1N HCl (1 mL), and EtOAc (10 mL). Load the mixture onto a Varian ChemElut CE1005 solid-phase extraction cartridge (Varian part number 12198006), then elute, collect, and concentrate 50 mL EtOAc to give the crude product (59 mg) as a white solid. Purify on 8 g silica gel (50-60% EtOAc/hexanes) to afford 34 mg (62%) of the title compound as a white solid. MS (ES): m/z 425 (M+1), 469 (M+HCO2−); 1H NMR (CDCl3): δ 8.16 (s, 1H), 7.63 (d, 1H, J=1.3 Hz), 7.44 (dd, 1H, J=8.6, 1.5 Hz), 7.24 (d, 1H, J=8.5 Hz), 6.36 (s, 1H), 5.55 (d, 1H, J=7.9 Hz), 5.29 (td, 2H, J=24.7, 9.0 Hz), 4.41 (m, 1H), 3.96 (s, 3H), 3.13 (dd, 1H, J=15.4, 4.8 Hz), 2.80 (m, 2H), 2.68 (s, 3H), 2.62 (dd, 1H, J=15.6, 6.8 Hz), 2.30 (m, 1H), 2.14-1.97 (m, 2H), 1.14 (d, 6H, J=6.6 Hz).
Reaction SMILES: Cl.[NH:2]([C:4]1[CH:5]=[CH:6][C:7]2[S:11][CH:10]=[C:9]([CH3:12])[C:8]=2[CH:13]=1)N.O.Cl.[NH:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1>>[CH3:12][C:9]1[C:8]2=[C:13]3[C:4](=[CH:5][CH:6]=[C:7]2[S:11][CH:10]=1)[NH:2][C:19]1[CH2:20][CH2:21][NH:16][CH2:17][C:18]3=1
Reactant: Cc1csc2ccc(NN)cc12
Reactant: O=C1CCNCC1
Agent: Cl
Solvent: O
Product: Cc1csc2ccc3[nH]c4c(c3c12)CNCC4

Procedure:
The compound is formed analogously to that described in Example 2, from 5 g of 5-hydrazino-3-methylbenzothiophene hydrochloride and 5 g of 4-piperidone hydrochloride monohydrate. Melting point: 234° C.
Reaction SMILES: CO[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[N+:9]([O-:11])=[O:10].[N:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:23][CH2:22][CH:21]([CH2:24][NH2:25])[CH2:20][CH2:19]2)=[CH:14][CH:13]=1>>[N+:9]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:3]=1[NH:25][CH2:24][CH:21]1[CH2:20][CH2:19][N:18]([C:15]2[CH:16]=[CH:17][N:12]=[CH:13][CH:14]=2)[CH2:23][CH2:22]1)([O-:11])=[O:10]
Reactant: NCC1CCN(c2ccncc2)CC1
Reactant: COc1ccncc1[N+](=O)[O-]
Product: O=[N+]([O-])c1cnccc1NCC1CCN(c2ccncc2)CC1
Yield: 72.9 %

Procedure:
Using a similar procedure to that described in Example 4, Part A, 4-methoxy-3-nitropyridine (250 mg, 1.62 mmol), and 1-(4-pyridyl)piperidin-4-ylmethylamine (310 mg, 1.62 mmol) yielded 370 mg (73%) of the title compound.
Reaction SMILES: C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH:18]2[C:27]3[N:23]([C:24]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[N:25][N:26]=3)[C:22]3[CH:34]=[CH:35][CH:36]=[CH:37][C:21]=3[N:20]([CH2:38][C:39](=[O:50])[N:40]([CH:47]([CH3:49])[CH3:48])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:19]2=[O:51])=[N:9]1)=O)(C)(C)C.Cl>O1CCOCC1.CCOC(C)=O>[NH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH:18]2[C:27]3[N:23]([C:24]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[N:25][N:26]=3)[C:22]3[CH:34]=[CH:35][CH:36]=[CH:37][C:21]=3[N:20]([CH2:38][C:39]([N:40]([CH:47]([CH3:48])[CH3:49])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[O:50])[C:19]2=[O:51])=[N:9]1
Reactant: CC(C)N(C(=O)CN1C(=O)C(Cc2nn(C(=O)OC(C)(C)C)c3ccccc23)c2nnc(-c3ccccc3)n2-c2ccccc21)c1ccccc1
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CC(C)N(C(=O)CN1C(=O)C(Cc2n[nH]c3ccccc23)c2nnc(-c3ccccc3)n2-c2ccccc21)c1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 66.5 %

Procedure:
To a solution of 3-{6-[(isopropyl-phenyl-carbamoyl)-methyl]-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl}-indazole-1-carboxylic acid tert-butyl ester (391.9 mg, 0.674 mmol) in dioxane (8 mL) was added 4M HCl in dioxane (6 mL). The reaction was stirred at room temperature for 24 hours and was diluted with EtOAc. The organic solution was washed with aqueous NaHCO3 and brine, was dried (MgSO4), filtered and concentrated in vacuo. Purification by medium pressure chromatography eluting with a solvent gradient (EtOAc to 10% MeOH in EtOAc) provided 260.9 mg of 2-[4-(1H-indazol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamide as a racemic mixture. 1H NMR (CD3OD) δ 7.90 (d, 1H), 7.65 (d, 2H), 7.34-7.54 (m, 12H), 7.22 (t, 1H), 7.13 (t, 1H), 6.99 (d, 1H), 4.74 (m, 1H), 4.65 (d, 1H), 4.42 (t, 1H), 3.92-4.12 (m, 3H), 0.99 (m, 6H); MS 582.7 (M+1), 580.4 (M−1).
Reaction SMILES: C(OCCCCCCCCCCCC)(=O)C(C)=C.[C:19](O)(=O)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]/[CH:27]=[CH:28]\[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36].C(O)CCCCCCC/C=C\CCCCCCCC.C(O)CCCCCCCCCCC=CCC.C(N)(=O)CCCCCCC/C=C\CCCCCCCC>>[CH2:19]=[CH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: C=C(C)C(=O)OCCCCCCCCCCCC
Agent: CCC=CCCCCCCCCCCCO
Agent: CCCCCCCC/C=C\CCCCCCCC(N)=O
Product: C=CCCCCCCCCCCCCCCCC

Procedure:
Lauryl methacrylate; Acrylated castor oil; Acrylated ricinoleic acid; Methacrylated ricinoleic acid; Soya Bean Oil; Unsaturated fatty acids, e.g. Oleic acid, tallow fatty acid; Unsaturated fatty alcohols, e.g. Oleyl alcohol, pentadeca-12-ene-1-ol.; Oleamide; Triglycerides, e.g. tall oil, ting oil; Ethylenic unsaturated urethanes; Acrylic unsaturated urethanes; Air drying short oil alkyds; Alkyl and Aryl Esters of maleic anhydride, singly or in combination.
Reaction SMILES: [C:1]([NH:5][CH2:6][CH:7]([OH:26])[CH2:8][O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=[O:15])=[CH:12][C:11]=1[C:19]1[CH2:24][CH2:23][C:22](=[O:25])[NH:21][N:20]=1)([CH3:4])([CH3:3])[CH3:2].C1(Cl)C(=O)C(Cl)=C(Cl)C(=O)C=1Cl>C(O)CCC>[C:1]([NH:5][CH2:6][CH:7]([OH:26])[CH2:8][O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=[O:15])=[CH:12][C:11]=1[C:19]1[CH:24]=[CH:23][C:22](=[O:25])[NH:21][N:20]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)NCC(O)COc1ccc(C(=O)O)cc1C1=NNC(=O)CC1
Agent: O=C1C(Cl)=C(Cl)C(=O)C(Cl)=C1Cl
Solvent: CCCCO
Product: CC(C)(C)NCC(O)COc1ccc(C(=O)O)cc1-c1ccc(=O)[nH]n1

Procedure:
A mixture of 4-(3-t-butylamino-2-hydroxypropoxy)-3-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)benzoic acid, chloranil, and n-butanol, was heated under reflux to give 4-(3-t-butylamino-2-hydroxypropoxy)-3-(1,6-dihydro-6-oxo-3-pyridazinyl)benzoic acid.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)#[CH:2].C([Mg]Br)C.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[C:21](=[O:26])[C:22]([Cl:25])([F:24])[F:23]>CCOCC.C1COCC1>[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[C:21]([OH:26])([C:2]#[C:1][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:22]([Cl:25])([F:23])[F:24]
Reactant: Nc1ccc(Cl)cc1C(=O)C(F)(F)Cl
Reactant: C#Cc1ccccc1
Agent: CC[Mg]Br
Solvent: C1CCOC1
Solvent: CCOCC
Product: Nc1ccc(Cl)cc1C(O)(C#Cc1ccccc1)C(F)(F)Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 71.5 %

Procedure:
To a 100 mL, 3 necked, oven dried round bottomed flask, with a stirring bar, argon inlet, reflux condenser, and a septum was added ethynyl benzene (2.13 g, 20.83 mmol), dry THF (50 mL) and ethyl magnesium bromide (6.94 mL of a 3.0M solution in ether). This mixture was aged 2 h at ambient temperature then a solution of 1-(2-amino-5-chlorophenyl)-2-chloro-2,2-difluoroethanone (1.00 g, 4.17 mmol) in THF (6 mL) was added with a syringe. The resulting orange-red solution was stirred at ambient temperature for 21.5 h. The reaction was quenched by addition of 1N HCl (50 mL) then diluted with EtOAc. The solution was then made basic with concentrated NH4OH and the layers were separated. The organic phase was washed with water and brine. Drying (MgSO4), filtration, removal of the solvent in vacuo, and chromatography on silica gel using 20% EtOAc in hexane as eluant gave 1.02 g of (+/-) 2-(2-amino-5-chlorophenyl)-4-phenyl-1-chloro-1,1-difluoro-3-butyn-2-ol as an off white solid. 1H NMR (CDCl3): δ4.42 (br s, 2H), 5.10 (br s, 1H), 6.65 (d, 1H, J=8.5 Hz), 7.15 (dd, 1H, J=2.4, 8.5 Hz), 7.38 (m, 3H), 7.55 (m, 2H), 7.70 (d, J=2.4 Hz).
Reaction SMILES: [CH2:1]([O:8]C(N1CCC2C(CO)(C2)C1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)=[O:22].OS(O)(=O)=O.O=[Cr](=O)=O.CO>CC(C)=O.O>[CH2:2]([C:1]([OH:8])=[O:22])[CH2:7][CH2:6][CH2:5][CH2:4][CH3:3]
Reactant: CC(C)=O
Reactant: O=C(OCc1ccccc1)N1CCC2CC2(CO)C1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CO
Product: CCCCCCC(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 93 %

Procedure:
To a solution of the compound of Step 3 (580 mg, 2.22 mmol) in acetone (10 ml) was added Jones reagent (2.8 ml) at 0° C. The mixture was stirred at this temperature for 1 hour. After addition of methanol (5 ml), the reaction mixture was warmed to room temperature and diluted with water. The product was extracted into methylene chloride, and the combined organic layers were washed with brine and dried over magnesium sulfate. Removal of solvent in vacuo provided the title compound as a white solid, (570 mg, 2.1 mmol, 93% yield).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][C:23]([OH:25])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[Cl:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]2[S:65][C:64]([NH2:66])=[N:63][C:62]=2[CH3:67])=[CH:57][C:56]=1[S:68]([CH3:71])(=[O:70])=[O:69]>CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][C:23](=[O:25])[NH:66][C:64]1[S:65][C:61]([C:58]2[CH:59]=[CH:60][C:55]([Cl:54])=[C:56]([S:68]([CH3:71])(=[O:70])=[O:69])[CH:57]=2)=[C:62]([CH3:67])[N:63]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)NCCOCCOCCOCCOCCC(=O)O
Reactant: Cc1nc(N)sc1-c1ccc(Cl)c(S(C)(=O)=O)c1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: Cc1nc(NC(=O)CCOCCOCCOCCOCCNC(=O)OC(C)(C)C)sc1-c1ccc(Cl)c(S(C)(=O)=O)c1
Temperature: 25 °C

Procedure:
3-(2-{2-[2-(2-tert-butoxycarbonylamino-ethoxy)-ethoxy]-ethoxy}-ethoxy)-propionic acid (690 mg 1.9 mmol), EDAC (403 mg 2.1 mmol), HOBT (284 mg 2.1 mmol), NMM (420 uL 3.8 mmol) and 5-(4-chloro-3-methanesulfonyl-phenyl)-4-methyl-thiazol-2-ylamine (520 mg 1.7 mmol) were combined in dimethylformamide (16 ml) and stirred over night at room temperature. The solvent was removed under reduced pressure and the residue dissolved in dichloromethane (150 ml), washed with 1M HCl aqueous solution (50 ml) and saturated aqueous sodium hydrogen carbonate (50 ml), dried (Magnesium sulphate), filtered and evaporated. The residue was purified by flash chromatography using 50 g IST silica flash cartridge eluting with 0-2% methanol/dichloromethane to yield (2-{2-[2-(2-{2[5-(4-chloro-3-methanesulfonyl-phenyl)-4-methyl-thiazol-2-ylcarbamoyl]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethyl)-carbamic acid tert-butyl ester as an oil (1.1 g residual solvent present) 1H NMR (400 MHz CDCl3) 10.3 (br s, 1H), 8.2 (s, 1H), 7.6 (m, 2H), 7.2 (br s, 1H), 3.9 (t, 2H) 3.8-3.5 (br m, 14H), 3.3 (br m, 5H), 2.8 (t, 2H), 2.4 (s, 3H), 1.4 (s, 9H).
Reaction SMILES: [F:1][C@@H:2]1[CH2:6][N:5](C(OC(C)(C)C)=O)[C@@H:4]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[CH2:3]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C@@H:2]1[CH2:6][NH:5][C@@H:4]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[CH2:3]1
Reactant: CC(C)(C)OC(=O)N1C[C@@H](F)C[C@@H]1c1cccc(F)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Fc1cccc([C@H]2C[C@H](F)CN2)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of (2R,4S)-tert-butyl 4-fluoro-2-(3-fluorophenyl)pyrrolidine-1-carboxylate (I-5A) (890 mg, 3.14 mmol) in DCM (5 mL) at room temperature was added TFA (5 mL). The mixture was stirred at room temperature for 2 hours. All the solvents were removed under reduced pressure. The crude was extracted with EtOAc, washed with aqueous NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated to yield (2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidine (I-6). 1H NMR (400 MHz, CDCl3) δ 7.31-7.25 (m, 1 H), 7.15-7.10 (m, 2 H), 6.96-6.90 (m, 1 H), 5.29 (d, J=53.6 Hz 1 H), 4.50 (dd, J=9.6, 6.4 Hz, 1 H), 3.43-3.33 (m, 1 H), 3.31-3.28 (m, 1 H), 2.51 (ddd, J=21.2, 14.0, 6.4 Hz, 1 H), 2.23 (bs, 1 H), 1.79 (dddd, J=39.6, 14.4, 10.0, 4.4 Hz, 1 H). MS m/z 184.1 (M+1)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([Br:8])[C:5]([O:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][C:3]=1[N+:14]([O-])=O.[H][H]>C(O)C.[Pt](=O)=O>[F:1][C:2]1[CH:7]=[C:6]([Br:8])[C:5]([O:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][C:3]=1[NH2:14]
Reactant: [H][H]
Reactant: COC(=O)Oc1cc([N+](=O)[O-])c(F)cc1Br
Agent: O=[Pt]=O
Solvent: CCO
Product: COC(=O)Oc1cc(N)c(F)cc1Br
Yield: 106 %

Procedure:
Platinum dioxide (1.0 g) was added to a solution of 2-fluoro-4-bromo-5-methoxycarbonyloxinitrobenzene (30.4 g, 0.1 mol) in ethanol (300 ml) and the solution was stirred in normal atmospheric pressure of hydrogen until absorption of hydrogen was terminated. After completion of the reaction, the catalyst was removed by filtration and the solvent was removed by distillation from the filtrate to give a brown solid (28.0 g) of 2-fluoro-4-bromo-5-methoxycarbonyloxianiline.
Reaction SMILES: I[C:2]1[C:11]2[S:12][C:13]([CH3:16])=[C:14]([CH3:15])[C:10]=2[C:9]([C:17]2[CH:22]=[CH:21][C:20]([O:23]S(C)(=O)=O)=[CH:19][CH:18]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]2.[C:28]1([SH:34])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[OH-].[Na+].Cl>CN(C)C=O.O>[CH3:16][C:13]1[S:12][C:11]2[C:2]([S:34][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:3]3[C:8](=[C:9]([C:17]4[CH:18]=[CH:19][C:20]([OH:23])=[CH:21][CH:22]=4)[C:10]=2[C:14]=1[CH3:15])[CH:7]=[CH:6][CH:5]=[CH:4]3
Reactant: Sc1ccccc1
Reactant: Cc1sc2c(I)c3ccccc3c(-c3ccc(OS(C)(=O)=O)cc3)c2c1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1sc2c(Sc3ccccc3)c3ccccc3c(-c3ccc(O)cc3)c2c1C
Temperature: 155 °C
Reaction time: 8 h
Yield: 84.6 %

Procedure:
To a stirred suspension of methanesulfonic acid 4-(9-iodo-2,3-dimethyl-naphtho[2,3-b]thiophen-4-yl)-phenyl ester (0.620 g, 1.22 mmol), and copper I oxide (0.192 g, 1.34 mmol) in anhydrous N,N-dimethylformamide (10 mL) was added thiophenol (0.270 mL, 2.68 mmol) and finely ground sodium hydroxide (0.107 g, 2.68 mmol) under a dry argon atmosphere. The vessel was sealed and heated at 155° C. for 9.5 hours. After stirring at ambient temperature for about 8 hours the reaction mixture was poured into water, acidified with hydrochloric acid and the organics were extracted into ether. The extracts were combined, filtered, washed with water and concentrated. The yellow solid residue was dissolved in dioxane (8 mL) and a 2.5 N soduim hydroxide solution (4.5 mL) was added. The vial was sealed and heated at 102° C. When the reaction was done (as indicated by thin layer chromatography) the mixture was cooled to room temperature, diluted with water, and acidified with hydrochloric acid. The organics were extracted with ether, combined with silica gel and the solvents were removed. The adsorbate was flash chromatographed (gradient 90/10-85/15 petroleum ether/ethyl acetate) and the solvents were chased with benzene and petroleum ether to give the title compound as a white solid (0.426 g, 85%): NMR (DMSO-d6); δ9.70 (s, 1H, OH), 8.40 (d, J=8 Hz, 1H), 7.56-7.51 (m, 2H), 7.44-7.40 (m, 1H), 7.25-7.12 (m, 5H), 7.02 (d, J=7 Hz, 2H), 6.93 (d, J=9 Hz, 2H), 3.67 (s, 3H), 1.62 (s, 3H); MS(EI): [M+] 412 (100%); Anal. calc. for C26H20OS2: C, 75.69; H, 4.89; N, 0.00. Found C, 74.98; H, 4.86; N, 0.13.
Reaction SMILES: C([C:5]1[CH:6]=[CH:7][C:8](O)=[C:9]([C:11]2(C3C=CC=CC=3)[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][C:12]2=[O:20])[CH:10]=1)(C)(C)C.C1([Mg]Br)C=CC=CC=1.N1C2C(=CC=CC=2)C(=O)C1=[O:38]>C1COCC1>[OH:38][C:11]1([C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:10]=2)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][C:12]1=[O:20]
Reactant: CC(C)(C)c1ccc(O)c(C2(c3ccccc3)C(=O)Nc3ccccc32)c1
Reactant: O=C1Nc2ccccc2C1=O
Agent: Br[Mg]c1ccccc1
Solvent: C1CCOC1
Product: O=C1Nc2ccccc2C1(O)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 90 %

Procedure:
As another non-limiting example, 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3-dihydro-indol-2-one (compound 1181) was synthesized by adding dropwise a 1 M solution of phenylmagnesiumbromide (0.33 mole) to isatin (15 g, 0.1 mole) in 60 mL THF at 0° C. The resulting mixture was allowed to warm to room temperature and let stir at room temperature for 12 hours. The reaction mixture was quenched with a saturated solution of NH4Cl (100 mL) and diluted with 100 mL of dichloromethane. The layers were separated, the organic layer was washed with water followed by brine, dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to yield 20.1 g (90%) of 3-hydroxy-3-phenyl-1,3-dihydro-indol-2-one. A mixture of the above solid (2.5 g, 10 mmole), p-t-Bu-phenol (1.5 g, 10 mmol), p-toluenesulfonic acid (3 g) in 40 mL dichloroethane, was heated to 95° C. for six hours. The mixture was cooled and filtered. The filtrate was concentrated in vacuo to yield 2.4 g (66%) of the desired product (compound 1181).
Reaction SMILES: [CH3:1][C:2]1[C:7]([C:8]([O:10]CC)=[O:9])=[C:6]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=2)[N:5]=[C:4]([S:21][CH3:22])[N:3]=1.[OH-].[Na+].C(O)C>O>[CH3:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[C:6]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=2)[N:5]=[C:4]([S:21][CH3:22])[N:3]=1
Reactant: CCOC(=O)c1c(C)nc(SC)nc1Nc1cccc(C)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CSc1nc(C)c(C(=O)O)c(Nc2cccc(C)c2)n1
Temperature: 25 °C
Yield: 100.7 %

Procedure:
To a 100 ml round-bottom flask were added ethyl 4-methyl-6-[(3-methylphenyl)amino]-2-(methylthio)-5-pyrimidinecarboxylate (2.83 g, 8.92 mmole), sodium hydroxide (dissolved in 5 mL of water) (0.53 g, 13.4 mmole), ethanol (25 mL) and water (25 mL). The reaction was stirred at reflux for 2 h. It was cooled to room temperature and concentrated under vacuum. The residue was treated with water (100 mL) and acidified by dropwise addition of acetic acid. Ethyl acetate (500 mL) was then added and the mixture was stirred for 10 min. The organic phase was separated. The aqueous phase was extracted with ethyl acetate (2×) and the organic extracts were combined and washed with water, brine and dried over MgSO4. The solvent was removed under vacuum to yield the product (2.6 g).
Reaction SMILES: F[C:2](F)(F)CC[Mg]Br.[O:9]1[C:13]2[CH:14]=[CH:15][C:16]([C:18](=[O:20])[CH3:19])=[CH:17][C:12]=2[O:11][CH2:10]1>O1CCCC1>[O:9]1[C:13]2[CH:14]=[CH:15][C:16]([C:18]([OH:20])([CH3:2])[CH3:19])=[CH:17][C:12]=2[O:11][CH2:10]1
Reactant: FC(F)(F)CC[Mg]Br
Reactant: CC(=O)c1ccc2c(c1)OCO2
Solvent: C1CCOC1
Product: CC(C)(O)c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 4 h
Yield: 96 %

Procedure:
In a 500 milliliter, three-necked oven-dried round bottom flask equipped with a magnetic stirrer and charged with 200 milliliters of 0.50 M (3,3,3-trifluoropropyl)magnesium bromide in tetrahydrofuran was added 16.4 grams (0.1 mole) of 1-(benzo[d][1,3]dioxol-5-yl)ethanone, and the mixture was stirred at room temperature for 4 hours. The reaction was quenched by slowly pouring the mixture into 400 milliliters saturated ammonium chloride solution and extracted into 400 milliliters of ethyl acetate, and washed with brine then water to a neutral pH. The ethyl acetate extracts were then dried over sodium sulfate, filtered and concentrated in the rotary evaporator affording 17.28 grams of 2-(benzo[d][1,3]dioxol-5-yl)propan-2-ol (˜96% yield) as an amber oil which was used without further purification. 17 grams (0.096 mole) 2-(benzo[d][1,3]dioxol-5-yl)propan-2-ol and 11.6 grams (0.11 mole) of triethylamine were dissolved in 40 milliliters of methylene chloride and the resulting solution was slowly added to a flask equipped with magnetic stirrer and containing 11 milliliters (0.105 mole) of methacroyl chloride in 100 milliliters of dichloromethane cooled, which had been cooled to 0° C. The resultant mixture was slowly warmed to room temperature and allowed to stir for 12 hours. Upon completion of the reaction, confirmed by thin layer chromatography (TLC), the mixture was quenched by pouring it into 400 milliliters of deionized water, then extracting the product into methylene chloride. The methylene chloride extracts were then dried over sodium sulfate, filtered, and concentrated in the rotary evaporator affording 22.8 grams (˜72% yield) of 2-(benzo[d][1,3]dioxol-5-yl)-5,5,5-trifluoropentan-2-yl methacrylate as an amber oil. The oil was purified further by passing through a silica gel plug eluting with a 70/30 mixture of hexanes/methylene chloride affording 19 grams of the pure product. 1H NMR (500 MHz, Acetone-d6): δ 6.89-6.81 (m, Ar, 3H), 6.23 (s, 1H), 5.97 (s, 2H), 5.92 (s, 1H), 2.48-2.1 (m/m, 4H), 1.914 (s, 3H), 1.89 (s, 3H).