Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.[C:18]([Si:22]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)Cl)([CH3:21])([CH3:20])[CH3:19]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[Si:22]([O:7][CH2:6][C@H:5]1[O:8][C@@H:1]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:2][C@@H:3]1[OH:4])([C:18]([CH3:21])([CH3:20])[CH3:19])([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: Cc1cn([C@H]2C[C@H](O)[C@@H](CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)O2)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 48 h
Yield: 144.7 %

Procedure:
A mixture of thymidine (400 g, and 1.65 mol), 4-dimethylaminopyridine (0.8 g, 6.5 mmol) and t-butyldiphenylchlorosilane (347.2 g, 1.26 mol) in anhydrous pyridine (3.0 lt) was stirred at room temperature for 48 hr. To the stirred reaction mixture two lots of t-butyldiphenyl chlorosilane (129.4 g, 0.47 mol and 22.7 g, 0.082 mol) were added 12 hr. apart and stirring continued for an additional 48 hr. The reaction mixture was concentrated under vacuum and the residue redissolved in methanol (2.5 lt). The product was precipitated by pouring the reaction mixture into a cold stirred ice-water (5.0 lt) suspension. The aqueous suspension was stirred at room temperature for 3 hr. to quench traces of unreacted chlorosilane. The granular white precipitate was filtered and washed with distilled water (5×1 lt) and air dried to furnish 876 g of 5′-O-t-butyldiphenylsilyl thymidine (slightly contaminated with bissilyated product, about 5%). The impurity was removed by suspending finely powdered 5′-O-t-butyldiphenylsilyl thymidine in ether (600 ml) and pouring into stirred hexanes (1.5 lt).
Reaction SMILES: C[O:2][C:3](=[O:38])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:24](=[O:37])[N:25]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:26]=[C:27]([Cl:29])[CH:28]=2)=[CH:19][CH:18]=1)[NH:5][C:6]([C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:15])=[O:7].O.[OH-].[Li+].C(OCC)(=O)C>C1COCC1.O>[CH2:30]([N:25]1[CH:26]=[C:27]([Cl:29])[CH:28]=[C:23]([C:20]2[CH:19]=[CH:18][C:17]([CH2:16][C@@H:4]([C:3]([OH:38])=[O:2])[NH:5][C:6]([C:8]3[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=3[Cl:15])=[O:7])=[CH:22][CH:21]=2)[C:24]1=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: COC(=O)[C@H](Cc1ccc(-c2cc(Cl)cn(Cc3ccccc3)c2=O)cc1)NC(=O)c1c(C)cccc1Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1cccc(Cl)c1C(=O)N[C@@H](Cc1ccc(-c2cc(Cl)cn(Cc3ccccc3)c2=O)cc1)C(=O)O
Yield: 71.8 %

Procedure:
A solution of N-[(2-chloro-6-methylphenyl)carbonyl]-4-(1-benzyl-5-chloro-2-oxo-pyridinyl)-L-phenylalanine methyl ester (72 mg, 0.13 mmol) in THF (3 mL) was treated with a solution of lithium hydroxide monohydrate (22 mg, 0.52 mmol) in water (1.0 mL). Additional THF was added to effect a clear solution and the reaction mixture was stirred 1.5 hr at which time, TLC (ethyl acetate) indicated starting material was consumed. A few drops of acetic were added and the entire reaction mixture was applied to a 4×30 cm, C-18 reversed phase HPLC column and eluted with a linear gradient of acetonitrile in water of 5 to 95% over 35 min. The product containing fraction was lyophillyzed to give 4-(1-benzyl-5-chloro-2-oxo-3-pyridinyl)-N-[(2-chloro-6-methylphenyl)carbonyl]-L-phenylalanine (50 mg, 71%) as a white solid. LR-Electrospray: m/z negative ion 533 (M−H (2 Cl)); positive ion 557(M+Na), 552 (M+NH4), 535 (M+H (2 Cl)). HRMS: Obs. Mass 535.1190. Calcd. Mass 535.1191 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:8][C:9]=1[N:10]([C:17]([CH:19]1[CH2:24][CH2:23][CH:22]([CH3:25])[CH2:21][CH2:20]1)=[O:18])[CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)=[O:4].CCN(CC)CC.[CH3:39][N:40]=[C:41]=[O:42]>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[CH:8][C:9]=1[N:10]([CH:11]1[CH2:16][CH2:15][N:14]([C:41](=[O:42])[NH:40][CH3:39])[CH2:13][CH2:12]1)[C:17]([CH:19]1[CH2:20][CH2:21][CH:22]([CH3:25])[CH2:23][CH2:24]1)=[O:18])=[O:4]
Reactant: COC(=O)c1sc(-c2ccccc2)cc1N(C(=O)C1CCC(C)CC1)C1CCNCC1
Reactant: CN=C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CNC(=O)N1CCC(N(C(=O)C2CCC(C)CC2)c2cc(-c3ccccc3)sc2C(=O)OC)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 86.5 %

Procedure:
A solution of 3-[(4-methyl-cyclohexanecarbonyl)-piperidin-4-yl-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (145 mg, 0.33 mmol) in CH2Cl2 (3.3 mL) was treated with Et3N (69 mL, 0.49 mmol) and methyl isocyanate (28.2 mg, 0.49 mmol). After stirring at room temperature for 18 h, starting material remained. Methyl isocyanate (28.2 mg, 0.49 mmol) was added to the reaction that was stirred for another 4 h. The solvent was evaporated and the residue was dissolved in EtOAc, washed with HCl (0.1 M) and brine, dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography using (5% MeOH/CH2Cl2) to provide 3-[(1-Methylcarbamoyl-piperidin-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (142 mg, 87% yield). 1H NMR (CDCl3, 400 MHz): 7.65 (m, 2H), 7.45 (m, 3H), 7.00 (s, 1H), 4.78 (m, 1H), 4.35 (q, 1H), 4.05 (dd, 1H), 3.90 (m, 1H), 3.85 (s, 3H), 2.85 (m, 2H), 2.75 (d, 3H), 1.95 (m, 2H), 1.80 (m, 1H), 1.70-1.55 (m, 5H), 1.50-1.25 (m, 3H), 1.10 (m, 1H), 0.78 (d, 3H), 0.75-0.58 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23].O.ON1C2C=CC=CC=2N=N1.[Cl:38][C:39]1[CH:44]=[C:43]([Cl:45])[CH:42]=[C:41]([O:46][CH3:47])[C:40]=1[CH2:48][CH2:49][NH2:50].Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](=[O:18])[NH:50][CH2:49][CH2:48][C:40]3[C:41]([O:46][CH3:47])=[CH:42][C:43]([Cl:45])=[CH:44][C:39]=3[Cl:38])=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: COc1cc(Cl)cc(Cl)c1CCN
Reactant: CCOC(=O)C1CCOc2cc(Oc3ccc(C(=O)O)cc3)c(Cl)cc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C1CCOc2cc(Oc3ccc(C(=O)NCCc4c(Cl)cc(Cl)cc4OC)cc3)c(Cl)cc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 48.4 %

Procedure:
To a stirred solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1; 0.75 g; 2.0 mmol), 1-hydroxybenzotriazole hydrate, and 2-(2,4-dichloro-6-methoxyphenyl)ethanamine (Preparation 7; 0.48 g, 2.19 mmol) in 6 mL DMF at ambient temperature was added solid 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.46 g; 2.4 mmol). The resulting solution was stirred at ambient temperature overnight for convenience. The solution was diluted with 60 mL water and after stirring for 10 minutes, the mixture was transferred to a separatory funnel and extracted with 30 mL EtOAc. 1M HCl (30 mL) was added to enable layer separation. The organic layer was dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography on a Biotage 40M column, eluting with 70/30 hexane/EtOAc, to give 0.56 g of ethyl 6-chloro-7-(4-(2,4-dichloro-6-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylate as a white glass. MS (apci, pos) m/z=578.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[CH2:5][NH:6][C:7]1[C:12]([NH:13][C:14]([C:16]2[S:17][C:18]([CH3:21])=[CH:19][CH:20]=2)=O)=[CH:11][CH:10]=[CH:9][N:8]=1)[CH3:2].O>C(O)CO>[CH2:1]([O:3][C:4](=[O:22])[CH2:5][N:6]1[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:12]2[N:13]=[C:14]1[C:16]1[S:17][C:18]([CH3:21])=[CH:19][CH:20]=1)[CH3:2]
Reactant: CCOC(=O)CNc1ncccc1NC(=O)c1ccc(C)s1
Solvent: O
Solvent: OCCO
Product: CCOC(=O)Cn1c(-c2ccc(C)s2)nc2cccnc21
Yield: 0.9 %

Procedure:
A solution of N-[3-[(5-methyl-2-thienylcarbonyl)amino]-2-pyridinyl]glycine ethyl ester (93.8 g, 0.293 mole) in ethylene glycol (500 ml) was refluxed for 45 minutes and cooled. A 10-ml aliquot was taken (0.005 mole) and added to water. The product was extracted into ethyl acetate twice and the combined organic layer was washed twice with water, dried over magnesium sulfate, treated with charcoal, filtered, and evaporated under reduced pressure to give 0.8 g (53% yield) of solid. The solid was recrystallized from isopropyl alcohol/water to give 0.31 g of solid which was purified on a silica gel column using 1:1 methylene chloride/ethyl acetate as the eluting solvent. Evaporation of the solvent from the pure fraction and recrystallization of the resulting solid from isopropyl alcohol/water give title compound, mp 123°-125° C.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.[C:10]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]I)(=[O:13])[CH:11]=[CH2:12].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:10]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1)(=[O:13])[CH:11]=[CH2:12]
Reactant: C=CC(=O)OCCCCCCI
Reactant: OCc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=CC(=O)OCCCCCCOc1ccc(CO)cc1
Temperature: 60 °C
Reaction time: 3 h

Procedure:
A mixture consisting of 2.48 g of 4-hydroxybenzylalcohol, 5.64 g of 6-iodohexyl acrylate, and 2.76 g of potassium carbonate in 50 ml of DMF was stirred under nitrogen atmosphere for 3 h at 60° C. After being cooled to room temperature the reaction mixture was quenched with 100 ml 3N HCl and extracted with diethylether (2×100 ml). The combined ether extracts were washed with saturated NaCl solution, dried over sodium sulphate and concentrated to dryness to give 5.3 g of nearly pure 4-(6-acryloyloxyhexyloxy)benzylalcohol as a beige heavy oil.
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH3:21])=[CH:15][CH:14]=2)=[CH:7][C:6]=1[C@H:22]1[C@H:27]([OH:28])[C@@H:26]([OH:29])[C@H:25]([OH:30])[C@@H:24]([CH2:31][OH:32])[O:23]1)[CH:2]=[CH2:3].[H-].[Na+].[CH2:35](Br)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CN(C)C=O>[CH2:1]([O:4][C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH3:21])=[CH:15][CH:14]=2)=[CH:7][C:6]=1[C@H:22]1[C@H:27]([O:28][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C@@H:26]([O:29][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C@H:25]([O:30][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C@@H:24]([CH2:31][O:32][CH2:22][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:5]=2)[O:23]1)[CH:2]=[CH2:3]
Reactant: BrCc1ccccc1
Reactant: C=CCOc1cc(Cl)c(Cc2ccc(OCC)cc2)cc1[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCOc1cc(Cl)c(Cc2ccc(OCC)cc2)cc1[C@@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 200 %

Procedure:
To a solution of tetraol (13, 8.4 g, 18 mmol) from Step 2 in N,N-dimethylformamide (100 mL) at 0° C. under an atmosphere of nitrogen was added sodium hydride (60% dispersion in mineral oil, 10.1 g, 252 mmol), and the mixture was stirred for 30 min at the same temperature. Then benzyl bromide (19.5 mL, 162 mmol) was added dropwise, and the mixture was stirred with gradual warming to ambient temperature over 5 h. After re-cooling to 0° C., the reaction mixture was quenched by addition of water (100 mL). The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered and evaporated in vacuo. The resulting crude residue was purified on a Biotage® purification apparatus (silica gel, 5 to 20% tetrahydrofuran in hexanes gradient) to yield the title compound (19, 14.8 g, 18 mmol, 100%) as a white solid.
Reaction SMILES: COCCO[AlH2-]OCCOC.[Na+].[CH:13]1([NH:16][C:17]2[C:22]([C:23](N(OC)C)=[O:24])=[CH:21][N:20]=[C:19]3[N:29]([CH2:32][CH3:33])[N:30]=[CH:31][C:18]=23)[CH2:15][CH2:14]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1>[CH:13]1([NH:16][C:17]2[C:22]([CH:23]=[O:24])=[CH:21][N:20]=[C:19]3[N:29]([CH2:32][CH3:33])[N:30]=[CH:31][C:18]=23)[CH2:14][CH2:15]1
Reactant: CCn1ncc2c(NC3CC3)c(C(=O)N(C)OC)cnc21
Agent: COCCO[AlH2-]OCCOC
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCn1ncc2c(NC3CC3)c(C=O)cnc21
Reaction time: 0.17 h

Procedure:
Toluene was cooled at −19 to −20° C. and vitride (0.50 ml, 0.0034 mole) was added. After about 10 minutes, 4-(cyclopropylamino)-1-ethyl-N-methoxy-N-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide (500 mg, 0.0017 mole) was added and the reaction mixture was stirred for about 4 hours. Citric acid (10%) solution was added dropwise to quench the reaction and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate and concentrated in vacuo to give an oily compound. Yield: 300 mg. m/z: (M++1) 231.1.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([O:15]CC)=[O:14])=[CH:9]2)([O-:3])=[O:2].O.[OH-].[Li+].Cl>O1CCCC1.O>[N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([OH:15])=[O:14])=[CH:9]2)([O-:3])=[O:2]
Reactant: CCOC(=O)c1cc2cccc([N+](=O)[O-])c2[nH]1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cc2cccc([N+](=O)[O-])c2[nH]1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Commercially available ethyl 7-nitroindole-2-carboxylate (500 mg, 2.14 mmol) was dissolved in a solvent mixture of tetrahydrofuran and water (1:1, 20 mL). Lithium hydroxide hydrate (448 mg, 10.7 mmol) was added thereto, and the mixture was stirred for 8 h at room temperature. 1N-hydrochloric acid solution was added, and the reaction mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled under reduced pressure to give the title compound.
Reaction SMILES: [Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12](=[O:23])[C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:25]1[CH2:30][CH2:29][CH2:28][C@@H:27]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:26]1>CCCCO>[Br:1][C:2]1[C:3]([N:25]2[CH2:30][CH2:29][CH2:28][C@@H:27]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[CH2:26]2)=[C:4]2[C:10]([NH:11][C:12](=[O:23])[C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCCNC1
Reactant: O=C(Nc1c[nH]c2ncc(Br)c(F)c12)c1cccc(C(F)(F)F)c1
Solvent: CCCCO
Product: CC(C)(C)OC(=O)N[C@@H]1CCCN(c2c(Br)cnc3[nH]cc(NC(=O)c4cccc(C(F)(F)F)c4)c23)C1
Yield: 69 %

Procedure:
A mixture of N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-(trifluoromethyl)benzamide (250 mg, 0.622 mmol) and (R)-tert-butyl piperidin-3-ylcarbamate (374 mg, 1.87 mmol) in n-BuOH (3 mL) was processed as described in Example 62, Step B, to provide (R)-tert-butyl 1-(5-bromo-3-(3-(trifluoromethyl)benzamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (250 mg, 69% yield).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]([C:12]1[C:13]([CH3:18])=[N:14][O:15][C:16]=1[CH3:17])(OCC)=[O:8].S([O-])([O-])(=O)=O.[Na+].[Na+]>CCOCC>[CH3:18][C:13]1[C:12]([CH2:7][OH:8])=[C:16]([CH3:17])[O:15][N:14]=1
Reactant: CCOC(=O)c1c(C)noc1C
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: Cc1noc(C)c1CO

Procedure:
A suspension of 100 g (2.63 moles) of lithium aluminum hydride in 2.5 liters of anhydrous ether was stirred under nitrogen as a solution of 272 g. (1.61 mole) of the 4-carboethoxy-3,5-dimethylisoxazole prepared in Example 1 above in 400 ml. of anhydrous ether was added at such a rate as to maintain a gentle reflux. The suspension was stirred at room temperature under nitrogen overnight, during which time an extremely gummy green-gray mass formed in the bottom of the flask. The mixture was cooled in an ice bath and hydrolyzed with saturated aqueous sodium sulfate solution. Anhydrous sodium sulfate was added to dry the ether solution. The salts were removed by filtration and washed carefully with ether and chloroform. Solvent removal from the filtrates, finally at 50°/0.1 mm., gave a white crystalline mass. This was triturated with hot ether and then cooled. Filtration gave 3,5-dimethyl-4-hydroxymethyl-isoxazole as white prisms, m.p. 76.5°/77.5°. Concentration of the mother liquors gave a second crop of prisms, m.p. 76.5°-78°.
Reaction SMILES: I[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][NH:14][C:13](=[O:18])[CH:12]=[C:7]12.[Br-].[CH2:20]([Zn+])[CH2:21][CH3:22]>O1CCOCC1>[CH2:20]([C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][NH:14][C:13](=[O:18])[CH:12]=[C:7]12)[CH2:21][CH3:22]
Reactant: CCC[Zn+]
Reactant: O=C1C=C2c3cccc(I)c3CCN2C(=O)CN1
Agent: [Br-]
Solvent: C1COCCO1
Product: CCCc1cccc2c1CCN1C(=O)CNC(=O)C=C21
Temperature: 120 °C

Procedure:
90-1. To a degassed solution of 9-iodo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (1.0 g, 2.82 mmol) and propylzinc(II)-bromide (14.1 mL, 7.05 mmol, 0.5M in THF) in dioxane (28 mL) was added PEPPSI-iPr (0.29 g, 0.424 mmol) under argon and the mixture was heated in a pressure vessel at 120° C. for 2.5 h. The reaction mixture was allowed to warm to rt and the solvent was removed under reduced pressure. The residue was suspended in DCM/MeOH (9:1, v/v), filtrated through a pad of celite and the filtrate was evaporated under reduced pressure. The crude product was purified by flash-column chromatography over silicagel (Biotage Isolera Four, eluent: from 1% MeOH in DCM to 10% MeOH in DCM in 35 min) to yield the product as an oil. The title compound was crystallized from diethyl ether to afford yellow crystals (370 mg). UPLC-MS: MS 271.2 (M+H+); UPLC rt 0.86 min.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10]([C:14]([NH:16][C@@H:17]([CH2:22][CH2:23][S:24]([CH3:27])(=[O:26])=[O:25])[C:18]([O:20][CH3:21])=[O:19])=[O:15])=[CH:9][CH:8]=[CH:7]2)([O-])=O.C(O)C.[H][H]>C(OCC)(=O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10]([C:14]([NH:16][C@@H:17]([CH2:22][CH2:23][S:24]([CH3:27])(=[O:26])=[O:25])[C:18]([O:20][CH3:21])=[O:19])=[O:15])=[CH:9][CH:8]=[CH:7]2
Reactant: COC(=O)[C@H](CCS(C)(=O)=O)NC(=O)c1cccc2cc([N+](=O)[O-])ccc12
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: COC(=O)[C@H](CCS(C)(=O)=O)NC(=O)c1cccc2cc(N)ccc12

Procedure:
0.04 g of 10% palladium-on-charcoal is added to a solution of 0.42 g of methyl ester of methyl 2(S)-(6-nitro-1-naphthoylamino)-4-(methylsulphonyl)butanoate dissolved in 30 cm3 of ethyl acetate and 20 cm3 of ethanol and the solution is subjected to a hydrogen pressure of 1.5 atmosphere for 3 hours at a temperature in the region of 20° C. The reaction mixture is filtered on sintered glass covered with Celite and concentrated to dryness under reduced pressure. 0.6 g of methyl 2(S)-(6-amino-1-naphthoylamino)-4-(methylsulphonyl)-butanoate is obtained, the characteristics of which are the following:
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:5]=[CH:6][N:7]=1.O.C(=O)([O-])[O-].[Na+].[Na+].F[B-](F)(F)F.[C:30](P(C(C)(C)C)C(C)(C)C)(C)(C)[CH3:31]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:10]=[C:3]3[C:2]([CH:30]=[CH2:31])=[N:7][CH:6]=[CH:5][N:4]3[CH:8]=2)=[CH:12][CH:13]=1
Reactant: Fc1ccc(-c2cn3ccnc(Cl)c3n2)cc1
Reactant: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: [Pd]
Agent: F[B-](F)(F)F
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Solvent: O
Product: C=Cc1nccn2cc(-c3ccc(F)cc3)nc12
Temperature: 95 °C
Yield: 642.6 %

Procedure:
To a mixture of 8-chloro-2-(4-fluorophenyl)-imidazo[1,2-a]pyrazine (Example #6, Step A, 3.96 g, 16 mmol) in dioxane (80 mL) was added water (15.4 mL), sodium carbonate (EM Science, 5.08 g, 48 mmol), tri-t-butylphosphine tetrafluoroborate (Strem, 0.46 g, 1.6 mmol), and tris(dibenzylideneacetone)dipalladium(0) (0.73 g, 0.8 mmol). The reaction was degassed with nitrogen and then vinylboronic acid pinacolester (5.44 mL, 32 mmol) was added. The mixture was heated to about 95° C. for about 16 h. The reaction was cooled, EtOAc was added (250 mL), and the mixture was washed with water. The organic layer was dried over sodium sulfate, filtered, and evaporated. The residue was purified by FCC (33%-50% EtOAc/heptane). The residue was triturated with heptane and filtered to yield the title compound as a brown solid (2.46 g, 62%): LC/MS (Table 1, Method b) Rt=2.74 min; MS m/z: 240.3 (M+H)+.
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:7]=[CH:8][CH3:9].C=CC.[Mg]>C1C=CC=CC=1>[C:1]1([CH:8]([CH3:9])[CH3:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CC
Reactant: c1ccccc1
Agent: [Mg]
Product: CC(C)c1ccccc1

Procedure:
A benzene-propylene alkylation process which comprises contacting benzene with a propylene feedstock, at alkylation conditions comprising a temperature of from about 100° to 275° C., a pressure of from about 100 kPa to 13 MPa, and a liquid hourly space velocity of from about 0.5 to 50 hr-1, with a catalytic composition comprising a MgAPSO molecular sieve, said sieve comprising from about 0.003 to 0.035 mol fraction of magnesium in the microporous crystalline framework structure, to obtain a cumene product.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[C:7]([CH:27](OC)[O:28]C)[CH:8]=[C:9]2[C:17]=1[C:16](=[O:18])[C:15]1([O:20][C:21](=[O:23])[CH3:22])[O:19][N:10]2[CH2:11][CH:12]2[CH:14]1[N:13]2C(=O)C)(=[O:3])[CH3:2].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(Cl)(Cl)Cl>CC(C)=O>[C:1]([O:4][C:5]1[CH:6]=[C:7]([CH:27]=[O:28])[CH:8]=[C:9]2[C:17]=1[C:16](=[O:18])[C:15]1([O:20][C:21](=[O:23])[CH3:22])[O:19][N:10]2[CH2:11][CH:12]2[CH:14]1[NH:13]2)(=[O:3])[CH3:2]
Reactant: COC(OC)c1cc(OC(C)=O)c2c(c1)N1CC3C(N3C(C)=O)C(OC(C)=O)(O1)C2=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(C)=O
Solvent: ClC(Cl)Cl
Product: CC(=O)Oc1cc(C=O)cc2c1C(=O)C1(OC(C)=O)ON2CC2NC21
Temperature: 25 °C
Reaction time: 1 h
Yield: 20.9 %

Procedure:
To a solution of A-isomer of 11-acetyl-4-dimethoxymethyl-8-oxo-14-oxa-1,11-diazatetracyclo[7.4.1.02,7.010,12 ]tetradeca-2,4,6-trien-6,9-diyl diacetate (6 mg) in acetone (0.5 ml) was added p-toluenesulfonic acid (1 mg). The mixture was stirred for 1 hour at ambient temperature, and then subjected to preparative thin layer chromatography, which was developed with a mixture of chloroform and acetone (5:1, v/v) to afford A-isomer of 4-formyl-8-oxo-14-oxa-1,11-diazatetracyclo[7.4.1.02.7.010,12 ]tetradeca-2,4,6-trien-6.9-diyl diacetate (1 mg).