Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(C(C)C)CC)(C)C.[CH2:10]([C@@H:17]1[CH2:21][O:20][C:19](=[O:22])[N:18]1[C:23](=[O:29])[CH2:24]P(=O)([O-])[O-])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[Li+].[CH2:32]([O:39][CH2:40][CH:41]=O)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(#N)C>[CH2:10]([C@@H:17]1[CH2:21][O:20][C:19](=[O:22])[N:18]1[C:23](=[O:29])/[CH:24]=[CH:41]/[CH2:40][O:39][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=CCOCc1ccccc1
Reactant: O=C(CP(=O)([O-])[O-])N1C(=O)OC[C@H]1Cc1ccccc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: O=C(/C=C/COCc1ccccc1)N1C(=O)OC[C@H]1Cc1ccccc1
Temperature: 0 °C

Procedure:
Diisopropylethylamine (51 mL, 290 mmol) was added slowly to a mechanically stirred, 0° C. slurry composed of {2-[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-2-oxoethyl}phosphonate (94.8 g, 267 mmol; see Shapiro, G; Chengzhi, C. Tetrahedron Lett. 1992, 33, 2447) and dry lithium chloride (12.5 g, 280 mmol) in acetonitrile (260 mL). After stirring for 10 min, a solution of 2-benzyloxyacetaldehyde (40.0 g, 267 mmol) in acetonitrile (20 mL) was added dropwise over 10 min. The cooling bath was then removed and the reaction mixture was stirred at rt for 12 h before being partitioned between ether and water and the layers separated The aqueous phase was extracted with additional ether and the combined organic phases (700 mL total) were stirred at rt with 2M HCl (350 mL) for 1 h. The organic phase was then washed with saturated NaCl and NaHCO3 aqueous solutions, followed by drying over a mixture of Na2SO4 and MgSO4, and concentration in vacuo. Flash chromatography of the residue on silica gel eluting with 10/90 acetone/benzene yielded (4R)-4-benzyl-3-[(2E)-4-(benzyloxy)but-2-enoyl]-1,3-oxazolidin-2-one as a colorless solid upon trituration with ether. 1H NMR (500 MHz, d6-acetone) δ 7.57 (1H, d, J= 15.6 Hz), 7.43-7.27 (10H, m), 7.21-7.15 (1H, m), 4.84 (1H, t, J= 8.2 Hz), 4.64 (2H, s), 4.43 (1H, t, J= 8.5 Hz), 4.32 (2H, m), 4.29 (1H, dd, J= 2.9, 8.9 Hz), 3.24 (1H, dd, J= 3.1, 13.5 Hz), 3.03 (1H, dd, J= 8.4, 13.5 Hz).
Reaction SMILES: C(OC(=O)[NH:10][C:11]1([CH3:25])[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[N:19][CH:20]=[C:21]([C:23]#[N:24])[CH:22]=2)[CH2:13][CH2:12]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>C(O)(C)C.[Pd]>[NH2:10][C:11]1([CH3:25])[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[N:19][CH:20]=[C:21]([C:23]#[N:24])[CH:22]=2)[CH2:13][CH2:12]1
Reactant: CC1(NC(=O)OCc2ccccc2)CCN(c2cncc(C#N)c2)CC1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CC(C)O
Product: CC1(N)CCN(c2cncc(C#N)c2)CC1
Temperature: 90 °C
Reaction time: 18 h

Procedure:
To a stirred solution of (5′-cyano-4-methyl-3,4,5,6-tetrahydro-2H-(1,3′)bipyridinyl-4-yl)-carbamic acid benzyl ester (0.051 g, 0.15 mmol ) in isopropanol, (3.0 mL) at room temperature was added ammonium formate (0.050 g, 0.8 mmol) and 10% Pd/C (15 mg) under nitrogen. The reaction mixture was stirred at 90° C. for 18 hours, cooled, filtered through Celite and concentrated under reduced pressure to provide the titled compound. MS (CI) m/z 292 (M+1)+; 1H NMR (300 MHz, methanol-d4) δ ppm 8.48 (d, 1H), 8.18 (d, 1H), 7.65 (m, 1H), 3.49-3.36 (m, 2H), 3.32-3.36 (m, 2H), 1.73-1.61 (m, 4H), 1.20 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][C:11]([NH:40]C(=O)OC(C)(C)C)=[C:12]([C:14](=[O:39])[NH:15][C:16]2[CH:17]=[N:18][N:19]([CH3:38])[C:20]=2[N:21]2[CH2:30][CH2:29][C@@H:28]([NH:31]C(=O)C(F)(F)F)[C:24]3([CH2:27][CH2:26][O:25]3)[CH2:23][CH2:22]2)[N:13]=1.C(=O)([O-])[O-].[K+].[K+]>CO.O>[NH2:40][C:11]1[S:10][C:9]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])=[N:13][C:12]=1[C:14]([NH:15][C:16]1[CH:17]=[N:18][N:19]([CH3:38])[C:20]=1[N:21]1[CH2:22][CH2:23][C:24]2([O:25][CH2:26][CH2:27]2)[CH:28]([NH2:31])[CH2:29][CH2:30]1)=[O:39]
Reactant: Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2NC(=O)OC(C)(C)C)c1N1CC[C@@H](NC(=O)C(F)(F)F)C2(CCO2)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1N1CCC(N)C2(CCO2)CC1
Temperature: 65 °C
Reaction time: 0.33 h

Procedure:
To a solution of tert-butyl N-[2-(2,6-difluorophenyl)-4-[[1-methyl-5-[(10R)-10-[(2,2,2-trifluoroacetyl)amino]-3-oxa-7-azaspiro[3.6]decan-7-yl]pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (30 mg, 0.044 mmol) in methanol (2 mL) and water (2 mL) was added potassium carbonate (67 mg, 0.48 mmol). The mixture was heated at 65° C. for 8 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EA 3×. Combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was stirred with DCM (4 mL) and TFA (2 mL) for 20 min and concentrated under reduced pressure, basified with saturated NaHCO3, and extracted with ethyl acetate (3×). The combined organic layers were dried over MgSO4 and the solvent removed under reduced pressure and the residue purified by preparative HPLC to afford 510. LCMS (ES+) m/z 490 (M+1).
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][NH:3][C:2]1=[O:11].[Cl-].[Al+3].[Cl-].[Cl-].[C:16]([CH2:20][CH:21]([CH3:25])[C:22](Cl)=[O:23])([O:18][CH3:19])=[O:17]>C(=S)=S>[C:16]([CH2:20][CH:21]([CH3:25])[C:22]([C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[NH:1][C:2](=[O:11])[NH:3][CH2:4]2)=[O:23])([O:18][CH3:19])=[O:17]
Reactant: COC(=O)CC(C)C(=O)Cl
Reactant: O=C1NCc2ccccc2N1
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: COC(=O)CC(C)C(=O)c1ccc2c(c1)CNC(=O)N2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3,4-Dihydro-2(1H)-quinazolinone (3.6 g) is added to a stirred suspension of anhydrous aluminum chloride (16.5 g) in carbon disulfide (120 ml) under nitrogen. 3-Carbomethoxy-2-methyl-propionyl chloride (4 g) is added dropwise to the stirred suspension, and the reaction mixture refluxed for about 18 hours, cooled to RT and further cooled to 0° C. in an ice bath. The liquid phase is decanted and ice and cold water slowly added to the residue. The aqueous mixture is filtered and the filtered solid suspended and stirred in the anhydrous diethyl ether overnight. The suspension is filtered and the filtered solid used in the next step without further purification.
Reaction SMILES: C([N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([F:18])[CH:16]=2)[C:11]([CH:19]2[CH2:24][CH2:23][N:22]([C:25](OC3C=CC=CC=3)=O)[CH2:21][CH2:20]2)=[N:10]1)(=O)C1C=CC=CC=1.[OH-].[K+].Cl.FC1C=C2C([C:42](C3CCNCC3)=[N:43]N2)=CC=1.C([O-])(O)=O.[Na+].ClCC#N>C(O)C.C(#N)C.C(Cl)Cl.CCOC(C)=O>[F:18][C:15]1[CH:16]=[C:17]2[C:12]([C:11]([CH:19]3[CH2:20][CH2:21][N:22]([CH2:25][C:42]#[N:43])[CH2:23][CH2:24]3)=[N:10][NH:9]2)=[CH:13][CH:14]=1
Reactant: Fc1ccc2c(C3CCNCC3)n[nH]c2c1
Reactant: O=C(Oc1ccccc1)N1CCC(c2nn(C(=O)c3ccccc3)c3cc(F)ccc23)CC1
Agent: Cl
Agent: N#CCCl
Agent: O=C([O-])O
Solvent: ClCCl
Solvent: CC#N
Solvent: CCOC(C)=O
Product: N#CCN1CCC(c2n[nH]c3cc(F)ccc23)CC1
Temperature: 25 °C
Yield: 89.1 %

Procedure:
To a suspension of 1-benzoyl-6-fluoro-3-(1-phenoxycarbonyl-4-piperidinyl)-1H-indazole (31.6 g, 71.3 mmol) in ethanol (500 ml) was added 50% KOH(aq.) (100 g of KOH in 100 g H2O) at room temperature. The reaction mixture was warmed to reflux for 4 hours and cooled to room temperature. After adjusting the pH to about one (to litmus) using HCl (con., 110 ml), the volatiles were removed under reduced pressure. The remaining wet solid was diluted with water and collected via filtration. The solid material was dissolved into hot water to which 50% NaOH(aq.) was added (pH was about 10, to litmus). The precipitated 4-(6-fluoro-1H-indazol-3-yl)piperidine (10.7 g) was filtered and used without further purification. To a stirred suspension of 4-(6-fluoro-1H-indazol-3-yl)piperidine (4.95 g, 22.6 mmol) and NaHCO3 (2.1 g, 24.9 mmol) in dry acetonitrile (110 ml) was added chloroacetonitrile (1.6 ml, 24.9 mmol) at room temperature, under nitrogen. The suspension was warmed to reflux for 22.5 hours, cooled to room temperature, and subsequently filtered. The remaining solids were washed with DCM and the combined filtrates were concentrated. The resulting brown oil was dissolved into EtOAc and washed with water. The organic phase was dried (MgSO4), filtered and concentrated to give a brown solid which was re-dissolved into DCM/EtOAc and flushed through alumina with DCM. The eluent was concentrated to give 5.2 g of the desired product as a solid, m.p. 149°-151 ° C.
Reaction SMILES: [CH2:1]([C@:3]12[CH2:11][CH2:10][C@@H:9]3[C:12]4[CH2:13][CH:14]=[C:15]([O:20]C)[CH2:16][C:17]=4[CH2:18][CH2:19][C@H:8]3[C@@H:7]1[CH2:6][CH2:5][C:4]12OCC[O:22]1)[CH3:2].C(=O)(O)[O-].[Na+].CCOCC>C(O)(=O)C.O>[CH2:1]([C@:3]12[CH2:11][CH2:10][C@@H:9]3[C@@H:12]4[C:17]([CH2:18][CH2:19][C@H:8]3[C@@H:7]1[CH2:6][CH2:5][C:4]2=[O:22])=[CH:16][C:15](=[O:20])[CH2:14][CH2:13]4)[CH3:2]
Reactant: CC[C@]12CC[C@@H]3C4=C(CC[C@H]3[C@@H]1CCC21OCCO1)CC(OC)=CC4
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Solvent: CC(=O)O
Product: CC[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CCC2=O
Yield: 12 %

Procedure:
Heat 13β-ethyl-3-methoxy-17,17-ethylenedioxy-gona-2,5(10)-diene (0.1 g.) in glacial acetic acid (2.5 cc.) and water (1 cc.) on a steam bath for 20 minutes, bring finally to boiling and allow to cool. Add aqueous sodium bicarbonate to neutralize the solution and ether extract the product. Wash, dry and evaporate the ether extracts to furnish a residue (0.065 g.); crystallize from a mixture of acetone and light petroleum to obtain the title compound (0.01 g.), m.p. 154°-5°; ultraviolet absorption peak at 239 mμ (ε15,000); infrared absorption peaks at 5.75, 5.96 μ.
Reaction SMILES: [Cr:1].[S:2](=[O:6])(=[O:5])([OH:4])[OH:3].C(O)C.[S:10]([O-:14])([O-:13])(=[O:12])=[O:11].[NH2:15][C@H:16]([C:21]([OH:23])=[O:22])[CH2:17][CH2:18][S:19][CH3:20]>>[S:2]([O-:6])([O-:5])(=[O:4])=[O:3].[NH2:15][C@H:16]([C:21]([OH:23])=[O:22])[CH2:17][CH2:18][S:19][CH3:20].[Cr+3:1].[S:10]([O-:14])([O-:13])(=[O:12])=[O:11].[S:2]([O-:6])([O-:5])(=[O:4])=[O:3].[Cr+3:1]
Reactant: [Cr]
Reactant: O=S(=O)(O)O
Agent: CSCC[C@H](N)C(=O)O
Agent: O=S(=O)([O-])[O-]
Solvent: CCO
Product: [Cr+3]

Procedure:
Two grams of chromium plus 6 oxide (0.02 mol) is reacted with 0.03 moles of sulphuric acid in the presence of 0.04 moles of ethyl alcohol. The chromium plus 6 oxide is reduced to chromium plus 3 sulphate. The reaction mixture is heated and boiled until the solution turns green and no odor of acctaldehyde is given off. Thereafter 2.98 grams of L methionine is added and the mixture is heated on a steam bath until a dark green colored paste forms. The mixture is dried in a hot air oven and instrumental, and quantitative analysis as pre-viously described reveals the presence of a 1:1 L-form complex chromium methionine sulphate salt.
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)[CH:13]=[N:12]2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:30][C:31]1[CH:35]=[CH:34][N:33]([CH2:36][C:37]([CH3:40])([OH:39])[CH3:38])[N:32]=1>>[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)[CH:13]=[N:12]2)[C:8]([NH:30][C:31]2[CH:35]=[CH:34][N:33]([CH2:36][C:37]([OH:39])([CH3:38])[CH3:40])[N:32]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C(O)C(CC1CCCC1)n1ncc(Oc2ccccc2N2CCCC2)cc1=O
Reactant: CC(C)(O)Cn1ccc(N)n1
Product: CC(C)(O)Cn1ccc(NC(=O)C(CC2CCCC2)n2ncc(Oc3ccccc3N3CCCC3)cc2=O)n1
Yield: 34 %

Procedure:
Using the method described in Example 17, 3-cyclopentyl-2-[6-oxo-4-(2-pyrrolidin-1-yl-phenoxy)-6H-pyridazin-1-yl]-propionic acid (Intermediate 51) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1) afforded 3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[6-oxo-4-(2-pyrrolidin-1-yl-phenoxy)-6H-pyridazin-1-yl]-propionamide as a yellow solid (0.50 g, 34%); ES+-HRMS m/e calcd for C29H38N6O4 [M+H+] 535.3028 found 535.3027. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.05 (s, 3H), 1.06 (s, 3H), 1.08 (m, 1H), 1.25-1.73 (m, 8H), 1.83 (m, 4H), 1.93 (m, 1H), 2.25 (m, 1H), 3.22 (m, 4H), 3.89 (s, 2H), 4.67 (s, 1H), 5.44 (dd, J=4.5, J=10.7 Hz, 1H), 5.54 (d, J=2.9 Hz, 1H), 6.39 (d, J=2.3 Hz, 1H), 6.79 (m, 1H), 6.89 (dd, Jo=8.3 Hz, Jm=1.1 Hz, 1H), 7.09 (dd, Jo=7.9 Hz, Jm=1.5 Hz, 1H), 7.19 (m, 1H), 7.52 (d, J=2.3 Hz, 1H), 8.12 (d, J=2.9 Hz, 1H), 10.80 (s, 1H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[C:5]#[N:6].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:20]1(B(O)O)[CH2:22][CH2:21]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:20]1([C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=2[O:10][CH3:11])[C:5]#[N:6])[CH2:22][CH2:21]1
Reactant: OB(O)C1CC1
Reactant: COc1ccc(C#N)cc1Br
Agent: [Pd+2]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: CC(=O)[O-]
Solvent: Cc1ccccc1
Product: COc1ccc(C#N)cc1C1CC1
Temperature: 80 °C

Procedure:
A mixture of 3-bromo-4-methoxybenzonitrile (8-1, 5.0g, 23.6 mmol, 1.0 eq), aqueous potassium phosphate tribasic (65.0 ml, 1.27 M, 3.5 eq), cyclopropylboronic acid (10.1 g, 118 mmol, 5.0 eq), Pd(OAc)2 (0.539 g, 2.36 mmol, 0.1 eq) and tricyclohexylphosphine (0.661 g, 2.36 mmol, 0.1 eq) was stirred in degassed toluene (103 ml) and heated to 80° C. for three hours. An additional amount of cyclopropylboronic acid (1.0 g, 1.16 mmol, 0.5 eq) was added and the solution was further heated for 16 hours at 80° C. to complete the reaction. The reaction mixture was cooled and partitioned between brine and EtOAc. The organic phase was dried over sodium sulfate, filtered and concentrated to give an orange oil. The oil was purified by normal phase column chromatography (0 to 10% EtOAc in hexanes) to afford the product (8-2) as a yellow oil. 1H NMR (CDCl3) δ 7.44 (dd, 1H, J=8.4, 2.0 Hz), 7.09 (d, 1H, J=2.0 Hz), 6.86 (d, 1H, J=8.4 Hz), 3.92 (s, 3H), 2.13 (m, 1H), 0.97 (m, 2H), 0.65 (m, 2H).
Reaction SMILES: C[O:2][C:3]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([C:18]([NH2:20])=[O:19])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=1.Cl>C1(C)C=CC=CC=1>[CH:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:18]([NH2:20])=[O:19])[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[C:3](=[O:2])[CH2:4][C:5]=2[CH:6]=1
Reactant: COC1=Cc2ccccc2N(C(N)=O)c2ccccc21
Agent: Cl
Solvent: Cc1ccccc1
Product: NC(=O)N1c2ccccc2CC(=O)c2ccccc21
Temperature: 50 °C
Reaction time: 0.5 h

Procedure:
The residue obtained in Example 2A was transferred to a 2 L 4-necked round bottom flask and 500 ml of 2N aqueous HCl was added at a temperature ranging from about 25° C. to about 30° C. The reaction mass was heated to a temperature ranging from about 80° C. to about 85° C. and maintained for between 4 to 5 hours. After completion of the reaction (detected by HPLC/TLC), the reaction mass was cooled to a temperature ranging from about 50° C., and 500 ml of toluene was charged to the reaction mass and maintained for 30 minutes at a temperature of about 50° C. The reaction mass was further stirred at a temperature ranging from about 25° C. to about 30° C. for about 30 minutes. The solids were filtered, separated, and then washed twice with 100 ml of toluene. The product was dried to get crude oxcarbazepine of 97-98% purity as determined by HPLC.
Reaction SMILES: [C:1]1([CH2:7][C:8](=O)[C:9]([O-:11])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:13][C@H](C([O-])=O)CC([O-])=O.[NH4+].[NH4+].CC1C(O)=C(C=O)C(COP(O)(O)=O)=CN=1>O>[NH2:13][C@H:8]([C:9]([OH:11])=[O:10])[CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: N[C@@H](CC(=O)[O-])C(=O)[O-]
Reactant: O=C([O-])C(=O)Cc1ccccc1
Agent: Cc1ncc(COP(=O)(O)O)c(C=O)c1O
Agent: [NH4+]
Solvent: O
Product: N[C@@H](Cc1ccccc1)C(=O)O

Procedure:
A batch type process wherein the catalyst compositions are stirred in from 0.01 to 0.5 molar (preferably 0.05 to 0.3 molar) solution of phenylpyruvate in the presence of 0.015 to 0.75 molar ammonium L-aspartate (preferably 0.075 to 0.5 molar) and 0.4 to 0.000001 mmolar pyridoxal 5-phosphate (preferably 0.04 to 0.0004 mmolar in water at 5.0 to 10.0 pH (preferably 7.5 to 9.5 pH) for periods of 1.0 to 100 hours (preferably 8 to 48 hours) at temperatures below 50° C. (preferably 20° to 40° C.). Broadly from 0.05 to 50 g of immobilized cells, preferably from 1.0 to 15 g, are used per 0.1 mole of starting phenylpyruvate. After the conversion, the catalyst compositions may be removed by filtration or the equivalent for reuse in converting fresh batches of phenylpyruvate solutions. The product solutions are obtained in a form suitable for conventional processing to isolate the L-phenylalanine (ion exchange chromotography, precipitation, filtration, washing, recrystallization, drying).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:13]3[C:14]([C:17]([OH:19])=O)=[CH:15][N:16]=[C:12]3[CH2:11][CH2:10]2)=[CH:5][C:4]=1[F:20])#[N:2].[Si:21]([O:38][C:39]1[CH:40]=[C:41]([CH2:45][CH2:46][CH2:47][CH2:48][NH2:49])[CH:42]=[CH:43][CH:44]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>>[Si:21]([O:38][C:39]1[CH:40]=[C:41]([CH2:45][CH2:46][CH2:47][CH2:48][NH:49][C:17]([C:14]2[N:13]3[CH:9]([C:6]4[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([F:20])[CH:5]=4)[CH2:10][CH2:11][C:12]3=[N:16][CH:15]=2)=[O:19])[CH:42]=[CH:43][CH:44]=1)([C:34]([CH3:35])([CH3:36])[CH3:37])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: N#Cc1ccc(C2CCc3ncc(C(=O)O)n32)cc1F
Reactant: CC(C)(C)[Si](Oc1cccc(CCCCN)c1)(c1ccccc1)c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)[Si](Oc1cccc(CCCCNC(=O)c2cnc3n2C(c2ccc(C#N)c(F)c2)CC3)c1)(c1ccccc1)c1ccccc1

Procedure:
Carboxylic acid from Step K, Example 5 (13.4 mg, 0.0496 mmol), amine from Step D (20.0 mg, 0.0496 mmol), EDC hydrochloride (19.0 mg, 0.0991 mmol), HOBT (13.4 mg, 0.0991 mmol), and N,N-diisopropylethylamine (0.0432 mL, 0.248 mmol) were stirred in dry, degassed DMF (1 mL) at 25° C. for 16 hours. The reaction was poured onto aq. NaHCO3 (10 mL) and extracted with methylene chloride (3×10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo to provide the title compound as a white solid.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[NH:5][C:4]([CH3:11])([CH3:10])[CH2:3]1.[O:12]1[CH2:31][CH:13]1[CH2:14][O:15][C:16](=[O:30])[C:17]1[C:18](=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:19]([O:21][CH2:22][CH:23]1[O:25][CH2:24]1)=[O:20]>>[OH:12][CH:13]([CH2:31][N:5]1[C:6]([CH3:8])([CH3:9])[CH2:7][CH:2]([OH:1])[CH2:3][C:4]1([CH3:11])[CH3:10])[CH2:14][O:15][C:16](=[O:30])[C:17]1[C:18](=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:19]([O:21][CH2:22][CH:23]([OH:25])[CH2:24][N:5]1[C:4]([CH3:11])([CH3:10])[CH2:3][CH:2]([OH:1])[CH2:7][C:6]1([CH3:9])[CH3:8])=[O:20]
Reactant: O=C(OCC1CO1)c1ccccc1C(=O)OCC1CO1
Reactant: CC1(C)CC(O)CC(C)(C)N1
Product: CC1(C)CC(O)CC(C)(C)N1CC(O)COC(=O)c1ccccc1C(=O)OCC(O)CN1C(C)(C)CC(O)CC1(C)C

Procedure:
A mixture of 20.0 g of 4-hydroxy-2,2,6,6-tetramethylpiperidine and 13.9 g of bis(2,3-epoxypropyl)phthalate was reacted following the procedure described in Example 5, to give the desired Compound No. 87 in the form of a white powder. The Compound had an Rf value of 0.24 on thin-layer chromatography on silica gel developed with a 20:4:2:1 by volume mixture of ethyl acetate, benzene, ethanol and triethylamine.
Reaction SMILES: ClCl.[Cl:3][C:4]1[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:5]=1[CH2:6][O:7][C:8]1[CH:9]=[C:10]([CH:24]=[CH:25][CH:26]=1)[O:11][CH2:12][C:13]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:14]=1[C:15]([O:17]C)=[O:16]>>[Cl:3][C:4]1[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:5]=1[CH2:6][O:7][C:8]1[CH:9]=[C:10]([CH:24]=[CH:25][CH:26]=1)[O:11][CH2:12][C:13]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:14]=1[C:15]([OH:17])=[O:16]
Reactant: COC(=O)c1c(C)cccc1COc1cccc(OCc2ccc(Cl)cc2Cl)c1
Agent: ClCl
Product: Cc1cccc(COc2cccc(OCc3ccc(Cl)cc3Cl)c2)c1C(=O)O

Procedure:
1H NMR (300 MHz, CDCl3) δ 7.40 (m, 2H), 7.34 (m, 2H), 7.24 (m, 2H), 7.17 (t, 1H), 6.59 (m, 3H), 5.19 (s, 2H), 5.03 (s, 2H), 2.45 (s, 3H). MS (ESI) 415 (M−H, Cl2 pattern). Prepared from methyl 2-[3-(2,4-dichloro-benzyloxy)-phenoxymethyl]-6-methyl-benzoate (example 6e).
Reaction SMILES: [CH3:1][S:2]([CH:5]([CH2:16][CH2:17][CH2:18][CH:19]([O:25]C(=O)C)[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([O:14]C)=[O:13])(=[O:4])=[O:3].CS(C(CC=CC(OC(=O)C)CCCCC)CCCCCCC(OC)=O)(=O)=O>>[CH3:1][S:2]([CH:5]([CH2:16][CH:17]=[CH:18][CH:19]([OH:25])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13])(=[O:3])=[O:4]
Reactant: CCCCCC(CCCC(CCCCCCC(=O)OC)S(C)(=O)=O)OC(C)=O
Agent: CCCCCC(C=CCC(CCCCCCC(=O)OC)S(C)(=O)=O)OC(C)=O
Product: CCCCCC(O)C=CCC(CCCCCCC(=O)O)S(C)(=O)=O

Procedure:
This compound is prepared by the procedure of Example 3, Step E, except that the methyl 8-methylsulfonyl-12-acetoxyheptadecanoate is replaced by an equivalent quantity of methyl 8-methylsulfonyl-12-acetoxy-10-heptadecenoate.
Reaction SMILES: [F:1][C:2]([F:34])([F:33])[C:3]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[N:20]=[C:21]([C:25]3[CH:26]=[C:27]([CH3:31])[CH:28]=[CH:29][CH:30]=3)[O:22][C:23]=1[CH3:24])[CH:13]([CH3:32])[CH2:12]2)([OH:8])[C:4]([F:7])([F:6])[F:5]>C1(C)C=CC=CC=1.O=[Mn]=O>[F:6][C:4]([F:5])([F:7])[C:3]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[N:20]=[C:21]([C:25]3[CH:26]=[C:27]([CH3:31])[CH:28]=[CH:29][CH:30]=3)[O:22][C:23]=1[CH3:24])[C:13]([CH3:32])=[CH:12]2)([OH:8])[C:2]([F:34])([F:33])[F:1]
Reactant: Cc1cccc(-c2nc(CN3c4ccc(C(O)(C(F)(F)F)C(F)(F)F)cc4CC3C)c(C)o2)c1
Agent: O=[Mn]=O
Solvent: Cc1ccccc1
Product: Cc1cccc(-c2nc(Cn3c(C)cc4cc(C(O)(C(F)(F)F)C(F)(F)F)ccc43)c(C)o2)c1
Temperature: 70 °C
Reaction time: 10 h
Yield: 97.7 %

Procedure:
To a solution of 32 mg (0.07 mmol) of 1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol (example 47) in 0.5 mL of toluene were added 29 mg (0.33 mmol) of MnO2 powder and the mixture was stirred at 70° C. for 10 hrs. Filtration and evaporation of the solvent gave 33 mg (quantitative) of 1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol, grey solid, MS: 483 (MH+).
Reaction SMILES: [Si]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:18])[N:13]=[C:12]2[C:19]1[N:24]=[C:23]2[C:25]([C:47]([O-:49])=[O:48])=[CH:26][N:27]([C:28]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:22]2=[N:21][CH:20]=1)(C(C)(C)C)(C)C.[CH3:50]CCC[N+](CCCC)(CCCC)CCCC.[F-].O>C1COCC1>[OH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:18])[N:13]=[C:12]2[C:19]1[N:24]=[C:23]2[C:25]([C:47]([O:49][CH3:50])=[O:48])=[CH:26][N:27]([C:28]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:22]2=[N:21][CH:20]=1
Reactant: CCCC[N+](CCCC)(CCCC)CCCC
Reactant: Cn1nc(-c2cnc3c(n2)c(C(=O)[O-])cn3C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(O[Si](C)(C)C(C)(C)C)ccc21
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2ncc(-c3nn(C)c4ccc(O)cc34)nc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 115.5 %

Procedure:
To a solution of 2-(5-(tert-butyldimethylsilyloxy)-1-methyl-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxylate (3.4 g, 4.9 mmol) in THF (25 mL) was added TBAF (6.42 mL, 12.85 mmol) at 0° C., after the addition was completed, the reaction mixture was warmed to room temperature and stirred for 0.5 hour, then H2O (25 mL) was added to the mixture extracted with EtOAc (100 mL), the organic layer was washed with H2O (100 mL), brine (100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give methyl 2-(5-hydroxy-1-methyl-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxylate (3.2 g, >100%) as a yellow solid. LCMS: (M+H)+=566; (M+Na)+=588.