Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH2:22])[N:20]=[C:15]2[CH:14]=1.C1N=[CH:35][N:34]([C:37](N2C=NC=C2)=[O:38])[CH:33]=1.CCN(C(C)C)C(C)C.CNC>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH:22][C:37](=[O:38])[N:34]([CH3:35])[CH3:33])[N:20]=[C:15]2[CH:14]=1
Reactant: COc1ccc2c(c1)c(-c1cc3nc(CN)cnc3n1COCC[Si](C)(C)C)cn2C
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CNC
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COc1ccc2c(c1)c(-c1cc3nc(CNC(=O)N(C)C)cnc3n1COCC[Si](C)(C)C)cn2C
Temperature: 25 °C
Reaction time: 1 h
Yield: 23.7 %

Procedure:
A flask was charged with (6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine (0.413 g, 0.944 mmol, Preparation #1.1), CDI (0.184 g, 1.13 mmol), DIEA (0.412 mL, 2.36 mmol) and THF (10 mL). The mixture was allowed to stir at rt for about 1 h. Dimethylamine (2.0 M in THF, 0.472 mL, 0.944 mmol) was added to the mixture. After about 4 h, additional dimethylamine (2.0 M in THF, 0.236 mL, 0.472 mmol) was added. After about 12 h, dimethylamine (2.0 M in THF, 0.236 mL, 0.472 mmol) was added. After about 8 h, the mixture was concentrated under reduced pressure and the residue was dissolved in DCM (10 mL). The organic solution was then washed with water (2×4 mL). The organic layer was dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with 0 to 10% MeOH/DCM to give 3-((6-(5-Methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)-1,1-dimethylurea (0.114 g, 24%): LC/MS (Table 2, Method b) Rt=2.62 min; MS m/z 509 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=[O:8])[C:5]([OH:11])=[CH:4][CH:3]=1.C1C(=O)N([I:19])C(=O)C1.C(OCC)(=O)C>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=[O:8])[C:5]([OH:11])=[C:4]([I:19])[CH:3]=1
Reactant: O=C1CCC(=O)N1I
Reactant: O=C(O)c1cc(Cl)ccc1O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(O)c1cc(Cl)cc(I)c1O
Temperature: 60 °C
Reaction time: 20 h

Procedure:
5-Chlorosalicylic acid (20 g, 115.8 mmol) is dissolved in DMF (100 mL). To this solution is added NIS (26.1 g, 116.0 mmol) which causes the reaction to warm up to 60° C. The reaction is stirred at room temperature for 20 hours. At this point ethyl acetate (100 mL) is added and the solution washed with 0.1N HCl (100 mL). The organic phase is then washed with water (3×100 mL), dried with sodium sulfate and evaporated under reduced pressure to yield 5-yield 5-chloro-3-iodosalicylic acid as off-white solid. (mp 160°-163° C.)
Reaction SMILES: OO.[H][H].[CH:5]1[C:18]2[C:17](=[O:19])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:20])[C:9]=2[CH:8]=[CH:7][CH:6]=1>>[CH:14]1[CH:15]=[C:16]2[C:17]([OH:19])=[C:18]3[C:9](=[C:10]([OH:20])[C:11]2=[CH:12][CH:13]=1)[CH:8]=[CH:7][CH:6]=[CH:5]3
Reactant: [H][H]
Reactant: O=C1c2ccccc2C(=O)c2ccccc21
Agent: OO
Product: Oc1c2ccccc2c(O)c2ccccc12

Procedure:
An anthraquinone process is known as an industrial hydrogen peroxide production process. In this process, an anthraquinone compound is dissolved in an organic solvent to obtain a working solution, and in a hydrogenation step the anthraquinone compound is reduced with hydrogen in the presence of a hydrogenation catalyst so as to produce an anthrahydroquinone compound. Next, in an oxidation step the anthrahydroquinone compound is converted back into the anthraquinone compound, with hydrogen peroxide being produced at the same time. The hydrogen peroxide in the working solution is separated out from the working solution by a process such as water extraction. The working solution from which the hydrogen peroxide has been extracted is returned into the hydrogenation step, whereby a cyclic process is formed.
Reaction SMILES: NCC(O)=O.[OH-].[Na+].[NH:8]1[CH:12]=[CH:11][N:10]=[C:9]1[C:13]([CH:15]([CH2:18][CH2:19][OH:20])[CH2:16][OH:17])=[O:14].C1C=[N+]([C@@H]2O[C@H](COP(OP(OC[C@H]3O[C@@H](N4C5N=CN=C(N)C=5N=C4)[C@H](O)[C@@H]3O)(O)=O)([O-])=O)[C@@H](O)[C@H]2O)C=C(C(N)=O)C=1.COC1C=CC(C=O)=CC=1>O.CC(C)=O.C(O)C.C(Cl)Cl>[NH:8]1[CH:12]=[CH:11][N:10]=[C:9]1[C:13]([C@H:15]1[CH2:18][CH2:19][O:20][C:16]1=[O:17])=[O:14]
Reactant: O=C(c1ncc[nH]1)C(CO)CCO
Agent: COc1ccc(C=O)cc1
Agent: NC(=O)c1ccc[n+]([C@@H]2O[C@H](COP(=O)([O-])OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](O)[C@@H]3O)[C@@H](O)[C@H]2O)c1
Agent: NCC(=O)O
Solvent: O
Solvent: ClCCl
Solvent: CCO
Product: O=C1OCC[C@@H]1C(=O)c1ncc[nH]1

Procedure:
Glycine (18.8 grams) is dissolved in 2 liters of deionized water, and the pH is adjusted by the addition of 10% sodium hydroxide to 9.0. 2-Imidazoyl-1,4-butanediol (10.0 grams) is dissolved in 150 ml of acetone added to the glycine solution with stirring, followed by the addition of β-NAD+ (Sigma, 0.5 grams). To the resulting solution is added horse liver alcohol dehydrogenase (Sigma, 250 mg, approximately 400 units). After the enzyme has dissolved the pH is readjusted to 9.0 with 10% sodium hydroxide, and the reaction mixture is stirred at 30° C. During the reaction, the pH is maintained at 9.0 with a pH-stat by the addition of 10% sodium hydroxide. Progress of the reaction is monitored by thin layer chromatography (Silica gel plates, eluent methylene chloride; visualization by dipping in a solution of 5% anisaldehyde in ethanol and heating). When the reaction is complete as judged by thin layer chromatography, the reaction mixture is adjusted to a pH of 13 with 10 M sodium hydroxide and then extracted 3 times with 250 ml of methylene chloride. The pH of the aqueous mixture is then adjusted to 3 with concentrated HCl, followed by continuous extraction with 1 liter of ethyl acetate for 24 hours. The ethyl acetate extract is dried over anhydrous magnesium sulfate and evaporated under reduced pressure to yield (2R)-2-imidazoylbutyrolactone as a yellowish solid.
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(O)(=[O:39])CCCCCCC/C=C\C/C=C\C/C=C\CC>>[OH:39][CH:13]([CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:12][CH2:11][CH:10]=[CH:9][CH2:8][CH:7]=[CH:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([OH:20])=[O:19]
Reactant: CC/C=C\C/C=C\C/C=C\CCCCCCCC(=O)O
Reactant: CCCCC/C=C\C/C=C\CCCCCCCC(=O)O
Product: CCCCCC(O)CCC=CCC=CCCCCC(=O)O

Procedure:
The same procedure as in Example 2 was repeated, except that linoleic acid was replaced by α-linolenic acid, whereby 13-hydroxy-6,9-octadecadienoic acid was obtained.
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH3:11].[Li]C(C)(C)C.CCCCC.[B:22](OC)([O:25]C)[O:23]C.C1COCC1.Cl>C(OCC)C>[CH3:1][O:2][CH2:3][O:4][C:5]1[C:6]([CH3:11])=[CH:7][CH:8]=[CH:9][C:10]=1[B:22]([OH:25])[OH:23]
Reactant: COB(OC)OC
Reactant: COCOc1ccccc1C
Agent: Cl
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CCCCC
Product: COCOc1c(C)cccc1B(O)O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 1-(methoxymethoxy)-2-methylbenzene in diethyl ether (0.3M) cooled at −60° C. tBuLi in pentane (1.7M, 1.4 eq) was added dropwise and the mixture was stirred for 1 h while warming gradually to 0° C. then for further 2 h at 0° C. The mixture was cooled to −78° C. and a solution of B(OMe)3 in THF (3 eq, 3.0M) was added dropwise and the mixture was allowed to reach RT and stirred overnight. The mixture was cooled to 0° C. and 1N HCl was added, then the reaction mixture was stirred for 2 h. All volatiles were removed under reduced pressure and the residue was extracted with EtOAc. The combined extracts were washed with H2O and brine, dried over Na2SO4, filtered and evaporated in vacuo to give a yellow solid which was triturated with PE to give a white solid which was used in the next step without further purification.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[NH:14][C:13](=[O:18])[N:12]([CH3:19])[C:11]=2[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:22]([O:25][C@H:26]([CH3:32])[CH2:27][CH2:28][CH2:29][CH2:30]Cl)(=[O:24])[CH3:23]>CS(C)=O>[C:22]([O:25][C@H:26]([CH3:32])[CH2:27][CH2:28][CH2:29][CH2:30][N:14]1[C:15](=[O:17])[C:16]2[N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:9]=[N:10][C:11]=2[N:12]([CH3:19])[C:13]1=[O:18])(=[O:24])[CH3:23]
Reactant: Cn1c(=O)[nH]c(=O)c2c1ncn2Cc1ccccc1
Reactant: CC(=O)O[C@H](C)CCCCCl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CC(=O)O[C@H](C)CCCCn1c(=O)c2c(ncn2Cc2ccccc2)n(C)c1=O
Temperature: 75 °C
Reaction time: 0.5 h
Yield: 84.6 %

Procedure:
To a stirring suspension of 7-benzyl-3-methylxanthine (25.6 g, 100 mmol) (which had been prepared as described for CT22404 of Example 18) in dimethylsulfoxide (200 ml) was added 95% sodium hydride (3.2 g, 133 mmol) in portions over 10 minutes. After stirring for 30 minutes, (R)-5-acetoxy-1-chlorohexane (19.63 g, 110 mmol) was added neat. After heating at 70-80° C. for 6 hours, the reaction mixture was quenched by addition of water (500 ml) and extracted with ethyl acetate (3×150 ml). The combined extracts were washed with water (150 ml), saturated aqueous sodium chloride solution (150 ml) and dried over magnesium sulfate. Evaporation of the solvent under reduced pressure gave a residue which was purified by flash chromatography on silica gel eluting with 20% hexane/ethyl according to give (R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthine (33.7 g).
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][CH2:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([CH2:13][CH2:14][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH3:16])[CH2:9][CH2:8]1)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[C:20]([O:19][C:17](=[O:18])[N:15]([CH2:14][CH2:13][C@H:10]1[CH2:9][CH2:8][C@H:7]([CH2:6][CH2:5][CH2:4][OH:3])[CH2:12][CH2:11]1)[CH3:16])([CH3:21])([CH3:23])[CH3:22]
Reactant: CCOC(=O)CC[C@H]1CC[C@H](CCN(C)C(=O)OC(C)(C)C)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CN(CC[C@H]1CC[C@H](CCCO)CC1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of trans-3-{4-[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-cyclohexyl}-propionic acid ethyl ester in 40 ml of tetrahydrofuran was added under ice-cooling 547 mg (14.0 mmol) of lithium aluminium hydride in small portions. The reaction mixture was then stirred for 1 hour at room temperature. To destroy the excess of lithium aluminium hydride, 50 ml of brine was added to the reaction mixture under ice-cooling. It was then partitioned between ether and water, the organic layer was dried over magnesium sulfate and concentrated under reduced pressure giving 3.35 g (100% over 2 stepts) nearly pure trans-{2-[4-(3-hydroxy-propyl)-cyclohexyl]-ethyl}-methyl-carbamic acid tert-butyl ester as colorless viscous oil, MS. 317 (MNH4+).
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[CH:23]=[CH:22][C:7]2[CH:8]=[C:9]([C:11]([NH:13][C@@H:14]3[CH:19]4[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]4)[CH2:15]3)=[O:12])[S:10][C:6]=2[CH:5]=1.C(N(CC)CC)C.[Cl:31][C:32]1[CH:37]=[C:36]([Cl:38])[CH:35]=[CH:34][C:33]=1[N:39]=[C:40]=[O:41]>C1COCC1>[ClH:31].[N:16]12[CH2:21][CH2:20][CH:19]([CH2:18][CH2:17]1)[C@@H:14]([NH:13][C:11]([C:9]1[S:10][C:6]3[CH:5]=[C:4]([NH:3][C:40]([NH:39][C:33]4[CH:34]=[CH:35][C:36]([Cl:38])=[CH:37][C:32]=4[Cl:31])=[O:41])[CH:23]=[CH:22][C:7]=3[CH:8]=1)=[O:12])[CH2:15]2
Reactant: O=C=Nc1ccc(Cl)cc1Cl
Reactant: Nc1ccc2cc(C(=O)N[C@H]3CN4CCC3CC4)sc2c1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(Nc1ccc2cc(C(=O)N[C@H]3CN4CCC3CC4)sc2c1)Nc1ccc(Cl)cc1Cl
Reaction time: 18 h

Procedure:
A solution of 40 mg (0.11 mmol) of 6-amino-N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzothiophene-2-carboxamide dihydrochloride in 2 ml of THF is mixed with 29.8 μl (0.21 mmol) of triethylamine and 40.2 mg (0.21 mmol) of 2,4-dichlorophenyl isocyanate. After 18 h at room temperature, the product is purified by preparative HPLC. The concentrated product fraction is dissolved in a mixture of acetonitrile and 1 N hydrochloric acid (5:1), again concentrated and dried under high vacuum. 25 mg (44.5% of theory) of the title compound are obtained.
Reaction SMILES: C(=O)(O)[O-].[Na+].[OH:6][C@H:7]1[CH2:11][NH:10][C@H:9]([C:12]([OH:14])=[O:13])[CH2:8]1.[CH2:15]([O:22][C:23](Cl)=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>O.C1(C)C=CC=CC=1>[CH2:15]([O:22][C:23]([N:10]1[CH2:11][C@H:7]([OH:6])[CH2:8][C@H:9]1[C:12]([OH:14])=[O:13])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: O=C(O)[C@@H]1C[C@@H](O)CN1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: O=C(O)[C@@H]1C[C@@H](O)CN1C(=O)OCc1ccccc1
Temperature: 28 °C
Reaction time: 3 h

Procedure:
Sodium bicarbonate (131.04 g) was dissolved in water (1040 ml), and trans-4-hydroxy-L-proline (78.6 g) was added thereto. To the resultant mixture, a solution of benzyloxycarbonyl chloride (72 ml) in dry toluene (320 ml) was added, and the mixture was stirred at an inner temperature of 28° C. for 3 hours. Sodium bicarbonate (65.52 g) and benzyloxycarbonyl chloride (72 ml) were additionally added thereto, and stirring was continued at the same temperature for 2 hours. The reaction mixture was washed with ether, and the aqueous layer was filtered. The filtrate was washed again with ether. The aqueous layer was adjusted to pH 1 with 6N hydrochloric acid and extracted with ethyl acetate. The extract was washed with aqueous sodium chloride solution, dried over sodium sulfate and concentrated to remove the solvent to give trans-1-benzyloxycarbonyl-4-hydroxy-L-proline.
Reaction SMILES: C(Cl)Cl.[C:4]1(OB(O)O)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[N:14]1[NH:15][N:16]=[N:17][C:18]=1[C:19]1[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH:24]=1.[OH-].[Na+]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(OCC)(=O)C.N1C=CC=CC=1>[C:4]1([N:15]2[N:16]=[N:17][C:18]([C:19]3[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH:24]=3)=[N:14]2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2nn[nH]n2)CC1
Reactant: OB(O)Oc1ccccc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1CC=C(c2nnn(-c3ccccc3)n2)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 10.2 %

Procedure:
Methylene chloride (2 ml), 60 mg of molecular sieves 4A, 12 mg of phenylboric acid, 8 μl of pyridine and 24 mg of copper(II) acetate were added to 12 mg of tert-butyl 4-(2H-tetrazol-5-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate prepared in 1) and the mixture was stirred at room temperature for 3 hours. After ethyl acetate and a 2N aqueous solution of sodium hydroxide were added thereto, the organic layer washed with a saturated aqueous solution of ammonium chloride and dried over sodium sulfate and the solvent was evaporated in vacuo. The resulting residue was purified by a silica gel thin-layer chromatography (hexane/ethyl acetate=3/1) to give 1.6 mg of the title compound as a crude product.
Reaction SMILES: Br[C:2]1[CH:21]=[CH:20][C:5]2[N:6]=[C:7]([N:9]3[CH2:13][CH2:12][C@@H:11]([N:14]4[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]4)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[CH3:22][O:23][C:24]1[N:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][N:25]=1.C1CCC(P(C2C(C3C=CC=CC=3)=CC=CC=2)C2CCCCC2)CC1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)C.O1CCOCC1>[CH3:22][O:23][C:24]1[N:29]=[CH:28][C:27]([C:2]2[CH:21]=[CH:20][C:5]3[N:6]=[C:7]([N:9]4[CH2:13][CH2:12][C@@H:11]([N:14]5[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]5)[CH2:10]4)[S:8][C:4]=3[CH:3]=2)=[CH:26][N:25]=1
Reactant: COc1ncc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: Brc1ccc2nc(N3CC[C@@H](N4CCCCC4)C3)sc2c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCO
Solvent: ClCCl
Product: COc1ncc(-c2ccc3nc(N4CC[C@@H](N5CCCCC5)C4)sc3c2)cn1
Temperature: 150 °C

Procedure:
A stirred mixture of (R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole (Example 14, 37.0 mg, 0.10 mmol), 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (31 mg, 0.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (7.0 mg, 0.01 mmol), (2-biphenyl)dicyclohexylphosphine (3.5 mg, 0.01 mmol) in 1:1 ethanol/dioxane (0.40 mL) was treated with 1 M aqueous sodium carbonate (0.150 mL, 0.15 mmol). The reaction tube was sealed and the stirred mixture was heated to 150° C. under microwave irradiation for 10 minutes. The reaction mixture was cooled to room temperature then diluted with dichloromethane (2 mL) and filtered through diatomaceous earth, followed by an acetonitrile/dichloromethane rinse (10 mL). The filtrate was dried (Na2SO4) and concentrated under reduced pressure and the residue was purified by silica gel chromatography (70:30:0 to 63:30:7 dichloromethane/acetonitrile/methanol). Fractions containing product were combined and concentrated under reduced pressure to give (R)-6-(2-methoxypyrimidin-5-yl)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole. 1H NMR (300 MHz, CD2Cl2) δ ppm 1.43-1.50 (m, 2H), 1.61 (pentet, J=5 Hz, 4H), 2.00 (pentet, J=10 Hz, 1H), 2.24-2.31 (m, 1H), 2.40-2.58 (m, 4H), 3.01 (pentet, J=8 Hz, 1H), 3.40 (t, J=9 Hz, 1H), 3.50-3.57 (m, 1H), 3.73 (t, J=9 Hz, 1H), 3.79-3.86 (m, 1H), 4.02 (s, 3H), 7.44 (dd, J=2, 8 Hz, 1H), 7.56 (d, J=8 Hz, 1H), 7.78 (d, J=2 Hz, 1H), 8.72 (s, 2H); MS (ESI) m/z 396 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]1[CH:14]([CH2:15][S:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:13][CH2:12][C:11]1=[O:23].ClC1C=CC=C(C(OO)=[O:33])C=1>>[CH3:1][O:2][C:3](=[O:24])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]1[CH:14]([CH2:15][S:16]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:33])[CH2:13][CH2:12][C:11]1=[O:23]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COC(=O)CCCCCCC1C(=O)CCC1CSc1ccccc1
Product: COC(=O)CCCCCCC1C(=O)CCC1CS(=O)c1ccccc1
Yield: 85 %

Procedure:
In accordance with the process of Example 29, 2-oxo-5-phenylthiomethyl-cyclopentaneheptanoic acid methyl ester of Example 27 (890 mg; 2.58 m mol) and m-chloroperbenzoic acid having a purity of 85% (5.25 mg; 2.58 m mol) were used to obtain 800 mg of 5-benzenesulfinylmethyl-2-oxo-cyclopentaneheptanoic acid methyl ester as viscous oil.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18](O)=[O:19])=[CH:13][CH:12]=1.C([O-])(=O)C.[Na+]>B(F)(F)F>[OH:2][C:1]1[CH:3]=[C:4]([OH:5])[CH:6]=[CH:7][C:8]=1[C:18](=[O:19])[CH2:17][C:14]1[CH:15]=[CH:16][C:11]([O:10][CH3:9])=[CH:12][CH:13]=1
Reactant: Oc1cccc(O)c1
Reactant: COc1ccc(CC(=O)O)cc1
Agent: CC(=O)[O-]
Agent: FB(F)F
Agent: [Na+]
Product: COc1ccc(CC(=O)c2ccc(O)cc2O)cc1
Temperature: 90 °C

Procedure:
Resorcinol (4.4 g, 40 mmol) and 4-methoxyphenylacetic acid (6.6 g, 40 mmol) in boron trifluoride.etherate (25 ml, 0.2 mol) was heated, under a nitrogen atmosphere, at 90° C. for ˜90 mins. to give a pale red solution. The solution was allowed to cool and poured into aqueous sodium acetate (200 ml, 10%) and the mixture stirred to give a pale yellow precipitate. The solids were removed by filtration and washed with water (200 ml). Solids were taken up in ethyl acetate (250 ml) and washed with water (200 ml). Solution was dried over anhyrous magnesium sulphate and concentrated, to a yellow semi-solid. Trituration with diethyl ether (100 ml) gave the 1-(2,4-dihydroxy-phenyl)-2-(4-methoxy-phenyl)-ethanone as a pale orange solid, dried in vacuo, (2.2 g) LC retention time 2.39 minutes [M+H]+ 259.2 (Run time 3.75 mins) N.M.R (DMSO-d6) 7.95(d J 8.9 Hz ArH) 7.2(d J 8.7 Hz 2ArH) 6.9(d J 8.7 Hz 2ArH) 6.4(d J 9.9 ArH) 6.25(s ArH) 4.2(s 2CH2) 3.75(s 3OCH3)
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8].[OH-].[Na+:11]>>[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O-:9])=[O:8].[Na+:11]
Reactant: NCCCCCC(=O)O
Agent: [Na+]
Agent: [OH-]
Product: NCCCCCC(=O)[O-]
Temperature: 15 °C

Procedure:
A jacketed 100 mL titration vessel was maintained at 15° C. by a circulating cooling bath. 6-Aminocaproic acid (10.416 g, 0.0794 mol, 2.1 equiv.) was dissolved in 20 mL of 14% aqueous NaOH (0.0794 mol, 2.1 equiv.) at 25° C. to form a solution of sodium 6-aminocaproate. The solution was placed into a 100 mL jacketed beaker which was maintained at 15° C. by a circulating cooling bath. Terephthaloyl chloride (7.674 g, 0.0378 mol, 1 equiv) was added in one portion and the reaction mixture stirred rapidly with a mechanical stirrer. The original pH of the solution was 12.8. As hydrochloric add was generated by the condensation of terephthaloyl chloride and sodium 6-aminocaproate, the pH began to fall. When the pH electrode in the solution sensed that the pH had dropped below the specified pH (in this case, pH=11.00), 14% NaOH was automatically titrated into the reaction to neutralize the hydrochloric acid. In this way the desired pH was maintained for the duration of the reaction. Completion of the reaction can be monitored visually by noting the disappearance of solid terephthaloyl chloride, or by uptake of sodium hydroxide with respect to the required theoretical amount. At the end of the reaction, the mixture was filtered through a bed of celite on a Buchner funnel to remove any unreacted terephthaloyl chloride. The product was precipitated by addition of 2.1 equivalents of 1 molar aqueous sulfuric acid isolated by filtration. The resulting white solid was washed with water to remove any residual NaCl, Na2SO4 or 6-aminocaproic acid. Typical yields: 90-93%.
Reaction SMILES: C[Mg]I.[F:4][C:5]1[C:28]([CH3:29])=[CH:27][C:8]2[N:9]([CH:13]3[CH2:18][CH2:17][N:16]([C:19]4([C:25]#N)[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)[CH2:15][CH2:14]3)C(=O)[O:11][C:7]=2[CH:6]=1>O1CCCC1>[F:4][C:5]1[C:28]([CH3:29])=[CH:27][C:8]([NH:9][CH:13]2[CH2:14][CH2:15][N:16]([C:19]3([CH3:25])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[CH2:17][CH2:18]2)=[C:7]([OH:11])[CH:6]=1
Reactant: Cc1cc2c(cc1F)oc(=O)n2C1CCN(C2(C#N)CCOCC2)CC1
Agent: C[Mg]I
Solvent: C1CCOC1
Product: Cc1cc(NC2CCN(C3(C)CCOCC3)CC2)c(O)cc1F
Temperature: 25 °C
Reaction time: 1 h
Yield: 17.1 %

Procedure:
Methylmagnesium iodide (3 mL, 9 mmol, 3 M in diethyl ether) was added to a suspension of 4-[4-(6-fluoro-5-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)-1-piperidinyl]tetrahydro-2H-pyran-4-carbonitrile (D4, 681 mg, 0.852 mmol) in tetrahydrofuran (10 mL) at 0° C. under argon. The reaction was stirred for 1 h at rt before being cooled to 0° C. and quenched with saturated aqueous NH4Cl (5 mL). The mixture was partitioned between ethyl acetate and water and the aqueous layer was extracted with ethyl acetate. The combined organics were dried (Na2SO4) and concentrated by rotary evaporation to give a brown oil, which was purified via chromatography (silica, dichloromethane to 0.5% ammonia/9.5% methanol/90% dichloromethane) to give a brown oil. This was further purified by high pH MDAP to give 5-fluoro-4-methyl-2-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-amino}phenol (D5, 47 mg 17% yield) as a brown solid.