Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C@@H:15]([OH:16])[C:14](=[O:17])[NH:13][C:12]3[CH:18]=[CH:19][CH:20]=[CH:21][C:11]=3[S:10]2)=[CH:5][CH:4]=1.[Cl:22][C:23]1[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26]>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[C@@H:15]([O:16][C:25](=[O:26])[C:24]3[CH:28]=[CH:29][C:30]([N+:32]([O-:34])=[O:33])=[CH:31][C:23]=3[Cl:22])[C:14](=[O:17])[NH:13][C:12]3[CH:18]=[CH:19][CH:20]=[CH:21][C:11]=3[S:10]2)=[CH:7][CH:8]=1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1Cl
Reactant: COc1ccc([C@@H]2Sc3ccccc3NC(=O)[C@@H]2O)cc1
Solvent: c1ccncc1
Product: COc1ccc([C@@H]2Sc3ccccc3NC(=O)[C@@H]2OC(=O)c2ccc([N+](=O)[O-])cc2Cl)cc1
Temperature: 0 °C
Yield: 99.3 %

Procedure:
3.01 g of (+)-cis-2-(4-methoxyphenyl)-3-hydroxy-2,3-dihydro-1,5-benzothiazepin-4(5H)-one are dissolved in 50 ml of pyridine, and 2.31 g of 2-chloro-4-nitrobenzoyl chloride are added thereto under ice-cooling and stirring. The mixture is stirred at room temperature overnight. The mixture is poured into ice-water and then extracted with ethyl acetate. The extract is washed with 10% hydrochloric acid and water, dried and then evaporated under reduced pressure to remove solvent. The residue is purified by silica gel chromatography (solvent, chloroform:methanol=100:1). 4.81 g of (-)-cis-2-(4-methoxyphenyl)-3-(2-chloro-4-nitrobenzoyloxy)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one are obtained as a pale yellow powder. Yield: 99%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:33]=[CH:32][C:6]([CH2:7][O:8][C:9]2[C:10]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][C:26]4=[O:31])=[CH:21][CH:20]=3)=[N:11][N:12]([CH3:18])[C:13]=2[C:14]([O:16]C)=[O:15])=[CH:5][CH:4]=1.O.[OH-].[Li+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9]2[C:10]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][C:26]4=[O:31])=[CH:21][CH:20]=3)=[N:11][N:12]([CH3:18])[C:13]=2[C:14]([OH:16])=[O:15])=[CH:32][CH:33]=1
Reactant: COC(=O)c1c(OCc2ccc(OC)cc2)c(-c2ccc(N3CCCCC3=O)cc2)nn1C
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1ccc(COc2c(-c3ccc(N4CCCCC4=O)cc3)nn(C)c2C(=O)O)cc1
Temperature: 120 °C

Procedure:
To a solution of methyl 4-(4-methoxybenzyloxy)-1-methyl-3-(4-(2-oxopiperidin-1-yl)phenyl)-1H-pyrazole-5-carboxylate T-21 (440 mg, 1.0 mmol) in methanol (10 mL) was added lithium hydroxide monohydrate (124 mg, 3.0 mmol). The reaction mixture was heated in a microwave reactor at 120° C. for 20 minutes. Solvent was removed under reduced pressure. Ethyl acetate and 0.1 N hydrochloric acid were added. The organic layer was washed with saturated brine. The organic layer was dried over sodium sulfate. Solvent was evaporated under reduced pressure. The crude product was purified by RP-HPLC to afford the desired 4-(4-methoxybenzyloxy)-1-methyl-3-(4-(2-oxopiperidin-1-yl)phenyl)-1H-pyrazole-5-carboxylic acid T-22 (100 mg, 0.23 mmol).
Reaction SMILES: C1N=C(N)C2N=CN([C@@H]3O[C@H](COP(OP(OC[C@H]4O[C@@H](N5C=C(C(N)=O)CC=C5)[C@H](O)[C@@H]4O)(O)=O)(O)=O)[C@@H](O)[C@H]3O)C=2N=1.C(=O)C.[CH3:48][N+:49]([CH2:52][C:53]([CH2:55][C:56]([OH:58])=[O:57])=[O:54])([CH3:51])[CH3:50].[Cl-]>C(O)(=O)C>[OH:54][C@H:53]([CH2:55][C:56](=[O:57])[O-:58])[CH2:52][N+:49]([CH3:51])([CH3:48])[CH3:50]
Reactant: C[N+](C)(C)CC(=O)CC(=O)O
Agent: CC=O
Agent: NC(=O)C1=CN([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)C=CC1
Agent: [Cl-]
Solvent: CC(=O)O
Product: C[N+](C)(C)C[C@H](O)CC(=O)[O-]
Reaction time: 24 h
Yield: 77.5 %

Procedure:
Carnitine was synthesized as in example 2, except that the NADH regeneration system comprised, in addition to alcohol dehydrogenase, aldehyde dehydrogenase (E.C. 1.2.1.5) which oxidizes the aldehyde (formed by action of alcohol dehydrogenase on ethanol) to acetic acid. Two molecules of NADH were formed from one molecule of ethanol (instead of one in the preceeding example) and the reaction balance was strongly displaced in favour of NADH and acetic acid formation. It was thus no longer necessary to eliminate acetaldehyde as in the preceeding example. The conditions were thus those of example 2, except that 125 units of purified aldehyde dehydrogenase (Boehringer ref. 171.832) were added to the reaction medium and nitrogen bubbling was omitted. After 24 hours, 0.764 g of L-carnitine was formed with a yield of 77.5% with respect to dehydrocarnitine hydrochloride.
Reaction SMILES: [C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][NH:3][NH:2]1.[CH3:12][N:13]1C(=O)O[C:16](=[O:17])[C:15]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:14]12>C1(C)C(C)=CC=CC=1>[CH3:12][NH:13][C:14]1[CH:24]=[CH:23][CH:22]=[CH:21][C:15]=1[C:16]([N:3]1[CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:1](=[O:11])[NH:2]1)=[O:17]
Reactant: Cn1c(=O)oc(=O)c2ccccc21
Reactant: O=C1NNCc2ccccc21
Solvent: Cc1ccccc1C
Product: CNc1ccccc1C(=O)N1Cc2ccccc2C(=O)N1
Temperature: 25 °C

Procedure:
To 3.3 g (0.022 ml) of 3,4-dihydro-phthalazin-1(2H)-one dissolved in 100 ml of xylene was added 3.9 g (0.022 mol) of N-methylisatoic anhydride and the solution was stirred and heated at reflux under N2 for 16 hours. The mixture was then cooled to room temperature (about 25° C.) whereupon a heavy precipitate formed. The 3-(o-methylaminobenzoyl)-3,4-dihydro-phthalazin-1(2H)-one was collected as a solid, washed well with xylene to give an off-white powder, mp 199°-202° C.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:15][CH2:14][N:13]3[CH2:16][CH:17]([CH2:20][OH:21])[CH2:18][CH2:19][CH:12]3[CH2:11]2)=[N:2]1.C(N(CC)CC)C.[CH3:29][S:30](Cl)(=[O:32])=[O:31].C(Cl)Cl.CO>C(Cl)Cl.[H+].[H+].[Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[I-].[Pt].O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:15][CH2:14][N:13]3[CH2:16][CH:17]([CH2:20][O:21][S:30]([CH3:29])(=[O:32])=[O:31])[CH2:18][CH2:19][CH:12]3[CH2:11]2)=[N:2]1
Reactant: CS(=O)(=O)Cl
Reactant: OCC1CCC2CN(c3noc4ccccc34)CCN2C1
Agent: [Pt]
Agent: [Cl-]
Agent: [H+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: CS(=O)(=O)OCC1CCC2CN(c3noc4ccccc34)CCN2C1
Temperature: 5 °C
Reaction time: 0.5 h
Yield: 90.2 %

Procedure:
To a chilled (5° C.) and stirred slurry of the alcohol title product of Example 7 (154.0 g, 0.54 mol) and triethylamine (81.76 ml, 59.6 g, 0.589 mol) in methylene chloride (3.0 liters), a solution of methanesulfonyl chloride (43.55 ml, 64.5 g, 0.563 mol) in methylene chloride (350 ml) was added dropwise over 30 minutes. TLC monitoring (methylene chloride/methanol=9:1 in volume; iodoplatinate spray) of the reaction mixture after an additional 1/2 hour of stirring indicated incomplete reaction. Complete reaction was realized within 1/2 hour after addition of a second portion of triethylamine (8.23 ml, 6.0 g, 59.3 mmol) and methanesulfonyl chloride (4.32 ml, 6.4 g, 55.9 mmol) added dropwise as a methylene chloride (20 ml) solution. Water (3 liters) and methylene chloride (1.5 liters) were added, and the biphasic mixture was vigorously stirred prior to separation of the organic and aqueous phases. The aqueous portion was then extracted with a fresh portion of methylene chloride (1.5 liters). The organic extracts were then combined, washed with brine (twice with 2 liter portions) and dried over anhydrous sodium sulfate. Concentration in vacuo afforded the present title compound as a tan solid (178.0 g, 90.2% yield). TLC Rf (methylene chloride/methanol=9:1 in volume; iodoplatinate spray): 0.24. MS m/z 365.1 (M, C17H23N3O4S). 13CNMR (CDCl3) delta 164.0, 160.9, 129.6, 122.4, 122.1, 116.0, 110.5, 71.9, 59.9, 57.7, 54.0, 53.3, 48.1, 37.4, 35.9, 28.4, 26.2.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=2)[CH:8]=[N:7][CH:6]=1.CC(C)([O-])C.[K+].C(O)(=O)C>O1CCCC1.CC(C)=O.Cl>[ClH:1].[C:17]([C:14]1[CH:15]=[CH:16][C:11]([CH:10]2[N:9]3[CH:8]=[N:7][CH:6]=[C:5]3[CH2:4][CH2:3][CH2:2]2)=[CH:12][CH:13]=1)#[N:18]
Reactant: N#Cc1ccc(Cn2cncc2CCCCl)cc1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CC(C)=O
Product: N#Cc1ccc(C2CCCc3cncn32)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 8.1 g of 5-(3-chloropropyl)-1-(p-cyanophenylmethyl)-1H-imidazole in 50 ml of tetrahydrofuran is cooled to 0°. To this is added 7.0 g of potassium t-butoxide as a solid in portions. The mixture is stirred at room temperature for 2 h, neutralized with 10% acetic acid and partitioned between methylene chloride and water. The organic layer is washed with water, dried over magnesium sulfate and evaporated to yield an oil which is dissolved in a small volume of acetone and neutralized with ethereal hydrogen chloride. On cooling, the title compound is obtained as a white solid, m.p. 201°-203°.
Reaction SMILES: Cl[C:2]1[C:7]([O:8][CH2:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:6][CH:5]=[CH:4][N:3]=1.[NH:18]1[CH2:24][CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>>[N:18]1([C:2]2[C:7]([O:8][CH2:9][CH2:10][O:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:6][CH:5]=[CH:4][N:3]=2)[CH2:24][CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1
Reactant: C1CNCCNC1
Reactant: Clc1nccnc1OCCOc1ccccc1
Product: c1ccc(OCCOc2nccnc2N2CCCNCC2)cc1

Procedure:
The title compound was prepared according to the procedure described in Example 4, Step 2, starting from 2-chloro-3-(2-phenoxyethoxy)pyrazine (150 mg, 0.60 mmol; from Example 1, Step 1) and homopiperazine (250 mg, 2.5 mmol) with the exception that a final extraction step between EtOAc and 5% aqueous NaOH was carried out. This gave 141 mg (75%) of the title product. Anal. (C17H22N4O2. 0.35EtOAc) C, H, N.
Reaction SMILES: [N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]([C:10]2[CH:15]=[CH:14][C:13]([C:16](=[O:20])[C:17]([OH:19])=O)=[CH:12][CH:11]=2)[CH:2]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[C:52]([C:56]1[CH:57]=[C:58]([NH2:68])[N:59]([C:61]2[CH:66]=[CH:65][C:64]([CH3:67])=[CH:63][CH:62]=2)[N:60]=1)([CH3:55])([CH3:54])[CH3:53]>CN(C=O)C>[C:52]([C:56]1[CH:57]=[C:58]([NH:68][C:17](=[O:19])[C:16]([C:13]2[CH:12]=[CH:11][C:10]([N:3]3[C:4]4=[N:5][CH:6]=[CH:7][CH:8]=[C:9]4[N:1]=[CH:2]3)=[CH:15][CH:14]=2)=[O:20])[N:59]([C:61]2[CH:62]=[CH:63][C:64]([CH3:67])=[CH:65][CH:66]=2)[N:60]=1)([CH3:55])([CH3:54])[CH3:53]
Reactant: Cc1ccc(-n2nc(C(C)(C)C)cc2N)cc1
Reactant: O=C(O)C(=O)c1ccc(-n2cnc3cccnc32)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)C(=O)c2ccc(-n3cnc4cccnc43)cc2)cc1
Reaction time: 4 h

Procedure:
A solution of (4-imidazo[4,5-b]pyridine-3-yl-phenyl)-oxo-acetic acid, HATU (104 mg, 0.27 mmol, 1.1 equiv) and triethylamine (0.102 mL, 0.73 mmol) in DMF (4 mL) is stirred for 5 minutes under N2. 5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-ylamine is then added and after 2 h, a further 1.2 equiv of HATU is added and after a further 2 h an additional 1.2 equiv of HATU is added. After 4 h, DMF is removed and the residue taken up in EtOAc and washed with 1N HCl, 1N NaOH and finally with brine. The organic layer is dried with MgSO4, filtered and concentrated. The residue is purified by MPLC on reverse phase with ACN/water to give N-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-2-oxo-acetamide as a yellow oil. Title compound: 479.05 [M+H]+; tR=1.9 min (System 2).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][NH:3][C:2]1=[O:7].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[N+:16]([C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Br)=[CH:21][CH:20]=1)([O-:18])=[O:17]>CN(C=O)C>[N+:16]([C:19]1[CH:26]=[CH:25][C:22]([CH2:23][N:1]2[CH2:6][CH2:5][CH2:4][NH:3][C:2]2=[O:7])=[CH:21][CH:20]=1)([O-:18])=[O:17]
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Reactant: O=C1NCCCN1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1NCCCN1Cc1ccc([N+](=O)[O-])cc1
Temperature: 100 °C
Reaction time: 2 h

Procedure:
To a solution of 3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (4 g, 0.04 mol) in abs. DMF (50 mL) there were added potassium carbonate (5.5 g, approximately 0.04 mol), potassium iodide (3.3 g, 0.02 mol), and 4-nitrobenzyl bromide (8.6 g, 0.04 mol) at RT. The reaction mixture was stirred at 100° C. over a period of 2 h. Following cooling of the reaction mixture, it was added to ice water (500 mL). The precipitated solid matter was filtered off in vacuo and washed with a little acetyl (4×10 mL). The desired product 1-(4-nitrobenzyl)tetrahydropyrimidin-2-one (H) was obtained as yellow solid matter (3.5 g, 40% of theory) having a melting point of 150-162° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[CH:10][N:11]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:28]([C:30]1[CH:31]=[C:32]([S:37](Cl)(=[O:39])=[O:38])[CH:33]=[CH:34][C:35]=1[F:36])#[N:29].[Cl-].[NH4+]>O1CCCC1>[C:28]([C:30]1[CH:31]=[C:32]([S:37]([N:6]([CH2:5][C:4]2[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=2[O:2][CH3:1])[C:7]2[S:8][CH:9]=[CH:10][N:11]=2)(=[O:39])=[O:38])[CH:33]=[CH:34][C:35]=1[F:36])#[N:29]
Reactant: COc1ccc(CNc2nccs2)c(OC)c1
Reactant: N#Cc1cc(S(=O)(=O)Cl)ccc1F
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc(F)c(C#N)c2)c(OC)c1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 25.8 %

Procedure:
N-(2,4-Dimethoxybenzyl)-1,3-thiazol-2-yl-amine (Preparation 91, 8.010 g, 0.032 mol) was dissolved in tetrahydrofuran (100 mL) and the solution was cooled to −78° C. Lithium hexamethyldisilazide in tetrahydrofuran (35.2 mL, 1M) was added dropwise to the reaction mixture. The cooling bath was removed and the reaction mixture was allowed to stir for 30 minutes to attain room temperature before re-cooling to −78° C. and a solution of 3-cyano-4-fluorobenzenesulfonyl chloride (7.028 g, 0.032 mol) in tetrahydrofuran (80 mL) was added dropwise to the reaction mixture. The reaction was allowed to stir 30 minutes at −78° C. before pouring it into saturated aqueous ammonium chloride (50 mL). The aqueous phase was separated and extracted with ethyl acetate (3×30 mL). The combined organic phases were washed twice with 10% aqueous citric acid solution (30 mL), water (30 mL), brine (20 mL), dried over MgSO4, filtered and evaporated. The residue was purified by column chromatography (120 g silica gel column, hexanes/ethyl acetate gradient elution 100/0 to 0/100). Product fractions were combined and evaporated. The residue was triturated with 10% tert-butyl methyl ether in hexanes and the resulting off-white solid collected by filtration and rinsed with hexanes and vacuum dried to provide the title compound (3.58 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7](OS(C(F)(F)F)(=O)=O)[CH:6]=[CH:5]2.[CH:20]([B-](F)(F)F)=[CH2:21].[K+].C(N(CC)CC)C.O>CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:20]=[CH2:21])[CH:8]=2)[CH:3]=1
Reactant: O=S(=O)(Oc1ccc2cc(Br)ccc2c1)C(F)(F)F
Reactant: C=C[B-](F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [K+]
Solvent: CCO
Solvent: O
Solvent: CCN(CC)CC
Product: C=Cc1ccc2cc(Br)ccc2c1
Temperature: 45 °C
Reaction time: 0.5 h
Yield: 96.5 %

Procedure:
A mixture of trifluoro-methanesulfonic acid 6-bromo-naphthalen-2-yl ester (2) (3.0 g, 8.45 mmol), potassium vinyltrifluoroborate (1.4 g, 11.83 mmol) in EtOH (84 mL) and a 1.0 M aqueous solution of cesium carbonate (17 mL) was purged with nitrogen, to the mixture was added tetrakis(triphenylphosphine)palladium (244 mg, 0.2 mmol) followed by triethylamine (2.3 mL, 17 mmol). The mixture was heated to 45° C. for 16 h under nitrogen and cooled to room temperature. To the mixture was added H2O (84 mL), the resulting suspension was stirred at room temperature for 30 min. and filtered. The wet cake was washed with H2O (30 mL) and dried in the vacuum oven at 45° C. for 16 h to give 1.9 g product. The product is used in the next step without further purification. 1H NMR (400 MHz, CDCl3) d 7.86 (d, 1H), 7.54–7.61 (m, 4H), 7.42–7.44 (dd, 1H), 6.73–6.80 (dd, 1H). 13C NMR (400 MHz, CDCl3) d 136.18, 135.12, 133.77, 131.62, 129.42, 129.32, 129.29, 126.93, 125.84, 124.00, 119.55, 114.54. [M+H]+ at m/z 233.
Reaction SMILES: C[O:2][C:3](=[O:26])[C:4](=[O:25])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][O:14][C:15]2[CH:24]=[CH:23][C:22]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[CH:16]=2)=[CH:7][CH:6]=1.[OH-].[Na+]>CO.O1CCCC1.O>[O:25]=[C:4]([C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][CH2:13][O:14][C:15]2[CH:24]=[CH:23][C:22]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[CH:16]=2)=[CH:9][CH:10]=1)[C:3]([OH:26])=[O:2]
Reactant: COC(=O)C(=O)c1ccc(OCCOc2ccc3c(c2)CCCC3)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C(=O)c1ccc(OCCOc2ccc3c(c2)CCCC3)cc1
Yield: 77.7 %

Procedure:
A mixture of alpha-oxo-4-[[2-(5,6,7,8-tetrahydro-2-naphthalenyloxy)ethyl]oxy]benzeneacetic acid methyl ester (0.75 g) in hot methanol (10 mL) plus enough tetrahydrofuran to dissolve all solids, was treated with 1N sodium hydroxide (4 mL) and diluted with water. The organic solvent was removed under vacuum and the residue was mixed with water, acidified with excess hydrochloric acid, and extracted with dichloromethane. The organic layer was dried (Na2SO4), filtered, and evaporated to give crude product. Crystallization from diethyl ether-hexane provided 0.56 g of alpha-oxo-4-[[2-(5,6,7,8-tetrahydro-2-naphthalenyloxy)ethyl]oxy]benzeneacetic acid as a colorless solid, mp 144°-145° C.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:36]=[CH:35][C:8]([CH2:9][NH:10][C:11]([C:13]2[C:14](=[O:34])[N:15]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)[C:16]([CH3:23])=[C:17]([C:19]([NH:21][NH2:22])=[O:20])[CH:18]=2)=[O:12])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[CH3:37][N:38]([CH3:42])[C:39](Cl)=[O:40]>C1COCC1>[CH3:37][N:38]([C:39]([NH:22][NH:21][C:19]([C:17]1[CH:18]=[C:13]([C:11]([NH:10][CH2:9][C:8]2[CH:35]=[CH:36][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:6][CH:7]=2)=[O:12])[C:14](=[O:34])[N:15]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:31])([F:33])[F:32])[CH:25]=2)[C:16]=1[CH3:23])=[O:20])=[O:40])[CH3:42]
Reactant: Cc1c(C(=O)NN)cc(C(=O)NCc2ccc(S(C)(=O)=O)cc2)c(=O)n1-c1cccc(C(F)(F)F)c1
Reactant: CN(C)C(=O)Cl
Solvent: C1CCOC1
Product: Cc1c(C(=O)NNC(=O)N(C)C)cc(C(=O)NCc2ccc(S(C)(=O)=O)cc2)c(=O)n1-c1cccc(C(F)(F)F)c1
Temperature: 50 °C
Reaction time: 3 h
Yield: 59.1 %

Procedure:
To 5-hydrazinocarbonyl-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide (0.030 g, 0.057 mmol) in THF (10 ml) was added N,N-dimethylcarbamoyl chloride (0.0247 g, 0.23 mmol) and the mixture was stirred at 50° C. for 3 h. The mixture was evaporated and the residue was purified by preparative HPLC giving 0.020 g (60%) of the title compound.
Reaction SMILES: [CH2:1]([O:4][CH2:5][CH:6]1[O:8][CH2:7]1)[CH:2]=[CH2:3].[CH2:9]([SiH:12]([O:15][CH3:16])[O:13][CH3:14])[CH:10]=[CH2:11]>C(O)(C)C.[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[CH3:14][O:13][Si:12]([O:15][CH3:16])([CH2:3][CH2:2][CH2:1][O:4][CH2:5][CH:6]1[O:8][CH2:7]1)[CH2:9][CH:10]=[CH2:11]
Reactant: C=CC[SiH](OC)OC
Reactant: C=CCOCC1CO1
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: C=CC[Si](CCCOCC1CO1)(OC)OC
Yield: 43023.8 %

Procedure:
Using the same apparatus and procedure described in EXAMPLE 1, 12.1 g (0.11 mmol) of allylglycidyl ether and 60 μl of 1% chloroplatinic acid in isopropanol were added to the flask. Through the dropping funnel was added dropwise 6.6 g (0.05 mmol) of allyldimethoxysilane at 80° C. and the solution was further reacted for 2 hrs to complete the reaction. Vacuum distillation (83°-85° C.) of the product mixture gave 5.3 g (43.5%) of 4,4-dimethoxy-7-glycidoxy-4-sila-1-heptene.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[C:12]1([O:18][CH2:19][C:20](=[CH2:22])[CH3:21])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCOCC.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[O:6]1[C:20]([CH3:21])([CH2:19][O:18][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:22]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=C(C)COc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Product: CC1(COc2ccccc2)CO1
Temperature: 25 °C
Reaction time: 5 h
Yield: 83 %

Procedure:
To a solution of 3-chloroperoxybenzoic acid (70% pure, 4.2 g, 17 mmol) in 40 mL of chloroform was added methallyl phenyl ether (2.5 g, 16.87 mmol). The mixture was stirred at room temperature for 5 hours then worked up by pouring into ether and sodium bicarbonate. The organic phase was washed with sodium bisulfite, sodium bicarbonate, and sodium chloride, dried over anhydrous sodium sulfate and evaporated to give 2.3 g of 1,2-epoxy-2-methyl-3-phenoxypropane.
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH2:14][CH2:13][CH:12]([N:15]2[CH:19]=[C:18]([I:20])[CH:17]=[N:16]2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1COCC1.[Li+].CC([N-]C(C)C)C.C1CCCCC1.[F:40]N(S(C1C=CC=CC=1)(=O)=O)S(C1C=CC=CC=1)(=O)=O.[NH4+].[Cl-]>>[Si:1]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[C:19]([F:40])=[C:18]([I:20])[CH:17]=[N:16]2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OC1CCC(n2cc(I)cn2)CC1
Reactant: O=S(=O)(c1ccccc1)N(F)S(=O)(=O)c1ccccc1
Agent: CC(C)[N-]C(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCCCC1
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)O[C@H]1CC[C@H](n2ncc(I)c2F)CC1
Reaction time: 0.5 h

Procedure:
A solution of 1-[4-(tert-butyl-dimethylsilanyloxy)-cyclohexyl]-4-iodo-1H-pyrazole (200.0 mg, 0.4922 mmol) in THF (2 mL, 20 mmol) was cooled to −78° C., and 1.5 M of LDA in cyclohexane (0.98 mL, 1.5 mmol) was added. After stirring for 30 min, N-fluoro-N-(phenylsulfonyl)benzenesulfonamide (620.8 mg, 1.969 mmol) was added slowly, and the mixture was stirred at −78° C. for 30 min. Sat. NH4Cl was added to quench, and the organic solvent was removed in vacuo. The material was extracted with DCM and water, and the organic layer was dry-loaded onto silica gel for column chromatography, eluting with 1% EtOAc/heptane. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a clear oil. MS (ES+): m/z=425.10 (100) [MH+]. HPLC: tR=2.22 min (polar—3 min, UPLC-ACQUITY).