Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][CH2:9][C@H:10]([C@H:21]([C@@H:23]([C@@H:25]([CH2:36][O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[O:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[CH:30][CH:29]=1)[OH:24])[OH:22])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>C1COCC1>[CH2:38]([O:37][CH2:36][C@H:25]([C@H:23]([C@@H:21]([C@@H:10]([CH2:9][O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][NH2:20])=[CH:15][CH:14]=1)[OH:22])[OH:24])[O:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][NH2:35])=[CH:30][CH:29]=1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1
Reactant: N#Cc1ccc(CO[C@H](COCc2ccccc2)[C@@H](O)[C@H](O)[C@@H](COCc2ccccc2)OCc2ccc(C#N)cc2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: NCc1ccc(CO[C@H](COCc2ccccc2)[C@@H](O)[C@H](O)[C@@H](COCc2ccccc2)OCc2ccc(CN)cc2)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 37 %

Procedure:
A stirred solution of 1,6-di-O-benzyl-2,5-di-O-(4-cyanobenzyl)-D-mannitol (100 mg, 0.17 mmol) (prepared in example 4) and lithium aluminum hydride (32 mg, 0.85 mmol) was heated at reflux for 3 h in THF. After cooling at room temperature, the reaction was treated with 2N sodium hydroxide and stirring was continued for a period of 5 h. The mixture was extracted with EtOAc and the extract was dried over magnesium sulfate and concentrated in vacuo. After purification by flash chrlomatography eluting with 10% MeOH in methylene chloride, the title compound was obtained in 37% yield.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=3[Cl:26])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[CH:6]=[CH:7][CH:8]=1.[C:27]([O-])([O-])=O.[K+].[K+].CI.O>CN(C=O)C>[Cl:26][C:20]1[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:19]=1[C:16]1[CH:15]=[CH:14][C:13]([S:10]([N:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([CH2:2][OH:1])[CH:4]=2)[CH3:27])(=[O:12])=[O:11])=[CH:18][CH:17]=1
Reactant: O=S(=O)(Nc1cccc(CO)c1)c1ccc(-c2ccc(Cl)cc2Cl)cc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CI
Solvent: CN(C)C=O
Product: CN(c1cccc(CO)c1)S(=O)(=O)c1ccc(-c2ccc(Cl)cc2Cl)cc1
Reaction time: 3 h

Procedure:
2′,4′-Dichlorobiphenyl-4-sulfonic acid-(3-hydroxymethyl-phenyl)-amide (ABD455) (0.4 g) was dissolved in DMF (20 ml). K2CO3 (1 g) was added followed by methyl iodide (1 ml). The mixture was stirred vigorously for 3 hrs, poured into water and extracted with ether. After drying (Na2SO4), the solvent was partially removed under vacuum and petrol added to induce crystallisation and the product collected as white crystals. 13C NMR (CDCl3): δ 38.4, 64.7, 125.3, 125.7, 126.0, 127.5, 127.7, 129.2, 129.8, 130.1, 131.9, 133.1, 134.9, 135.8, 137.2, 141.6, 142.0 and 142.8. 1H NMR (CDCl3): δ 3.22 (3H, s), 4.65 (2H, d, J=5.8 Hz), 7.02 (1H, m), 7.14 (1H, s), 7.28 (1H, s), 7.30 (3H, m), 7.48 (2H, d, J=8.2 Hz), 7.50 (1H, m) and 7.60 (2H, d, J=8.2 Hz).
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@@H:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C@H:14]1[C:26]1[CH:31]=[CH:30][C:29]([F:32])=[C:28]([Cl:33])[CH:27]=1.[Cl:34][C:35]1[CH:43]=[CH:42][C:38]([C:39](O)=[O:40])=[CH:37][CH:36]=1>>[Cl:33][C:28]1[CH:27]=[C:26]([C@H:14]2[C@H:13]([NH:12][C:39]([C:38]3[CH:42]=[CH:43][C:35]([Cl:34])=[CH:36][CH:37]=3)=[O:40])[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:15]2)[CH:31]=[CH:30][C:29]=1[F:32]
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](N)[C@H](c2ccc(F)c(Cl)c2)C1
Reactant: O=C(O)c1ccc(Cl)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: CC(C)(C)OC(=O)N1CC[C@@H](NC(=O)c2ccc(Cl)cc2)[C@H](c2ccc(F)c(Cl)c2)C1

Procedure:
sing the compound obtained in step 1 and 4-chlorobenzoic acid, and by the reaction and purification in the same manner as in Reference Example 1, step 5, the title compound was obtained.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[C:13]2[CH:12]=[C:11]3[C:14](=[CH2:24])[CH2:15][NH:16][CH2:17][CH2:18][N:19]([S:20]([CH3:23])(=[O:22])=[O:21])[C:10]3=[N:9][C:8]=2[O:7][C:6]=1[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)=[O:4].[CH3:32][S:33](Cl)(=[O:35])=[O:34].C(N(CC)CC)C>C(Cl)Cl>[CH3:1][NH:2][C:3]([C:5]1[C:13]2[CH:12]=[C:11]3[C:14](=[CH2:24])[CH2:15][N:16]([S:33]([CH3:32])(=[O:35])=[O:34])[CH2:17][CH2:18][N:19]([S:20]([CH3:23])(=[O:22])=[O:21])[C:10]3=[N:9][C:8]=2[O:7][C:6]=1[C:25]1[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=1)=[O:4]
Reactant: CS(=O)(=O)Cl
Reactant: C=C1CNCCN(S(C)(=O)=O)c2nc3oc(-c4ccc(F)cc4)c(C(=O)NC)c3cc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=C1CN(S(C)(=O)=O)CCN(S(C)(=O)=O)c2nc3oc(-c4ccc(F)cc4)c(C(=O)NC)c3cc21
Temperature: 0 °C
Yield: 44.2 %

Procedure:
2-(4-Fluoro-phenyl)-10-methanesulfonyl-5-methylene-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamide (6.0 mg, 0.013 mmol) is dissolved in DCM (2 mL) and the solution is cooled to 0° C. Methanesulfonyl chloride (7.7 mg, 0.07 mmol) is added followed by triethylamine (6.83 mg, 0.07 mmol) and the reaction is allowed to warm up to RT over 3 h then evaporated to dryness and placed on the high vacuum overnight. The sample is then redissolved in EtOAc (25 mL) and then washed with 1N HCl (10 mL), then Brine (20 mL) and dried over Na2SO4. The organic is concentrated to afford 2-(4-Fluoro-phenyl)-7,10-bis-methanesulfonyl-5-methylene-5,6,7,8,9,10-hexahydro-1-oxa-7,10,11-triaza-cycloocta[f]indene-3-carboxylic acid methylamide (3 mg, 42%). MS-ES [M+H]+=523.0.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[CH2:12][CH2:11][C:10]3[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:9]=3[CH:8]([N:18]3[CH2:23][CH2:22][N:21]([C:24](=[O:47])[CH2:25][CH:26]4[CH2:31][CH2:30][N:29]([C:32](=[N:40][S:41](=[O:46])(=[O:45])[N:42]([CH3:44])[CH3:43])OC5C=CC=CC=5)[CH2:28][CH2:27]4)[CH2:20][CH2:19]3)[C:5]2=[N:6][CH:7]=1.[OH-].[NH4+:49]>CC(O)C>[Br:1][C:2]1[CH:3]=[C:4]2[CH2:12][CH2:11][C:10]3[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:9]=3[CH:8]([N:18]3[CH2:23][CH2:22][N:21]([C:24](=[O:47])[CH2:25][CH:26]4[CH2:31][CH2:30][N:29]([C:32](=[NH:49])[NH:40][S:41](=[O:45])(=[O:46])[N:42]([CH3:44])[CH3:43])[CH2:28][CH2:27]4)[CH2:20][CH2:19]3)[C:5]2=[N:6][CH:7]=1
Reactant: CN(C)S(=O)(=O)N=C(Oc1ccccc1)N1CCC(CC(=O)N2CCN(C3c4ccc(Cl)cc4CCc4cc(Br)cnc43)CC2)CC1
Reactant: [NH4+]
Agent: [OH-]
Solvent: CC(C)O
Product: CN(C)S(=O)(=O)NC(=N)N1CCC(CC(=O)N2CCN(C3c4ccc(Cl)cc4CCc4cc(Br)cnc43)CC2)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Phenyl 4-[2-[4-(3-bromo-8-chloro-6,11-dihydro-5 H-benzo[5,6] cyclohepta[1,2-b]pyridin-11-yl)-1-piperazinyl]-2-oxoethyl]-N-(N,N-dimethyl-sulfamoyl)-l-piperidinecarboximidate (Formula 10.0, prepare as described in Example 9 above) is dissolved in 2-propanol and concentrated ammonium hydroxide is added. The mixture is stirred at 25° C. for 24 h and then evaporated to dryness. The residue is triturated with diethyl ether (2×250 ml) and the ether is discarded. The remaining product is chromatographed on a silica gel column to give the title compound (Formula 11.0).
Reaction SMILES: [CH3:1][N:2]([CH3:6])[CH2:3][CH2:4][NH2:5].[C:7]([NH:10][C:11]1[S:12][C:13]([S:17](Cl)(=[O:19])=[O:18])=[C:14]([CH3:16])[N:15]=1)(=[O:9])[CH3:8].C(N(CC)CC)C>O1CCCC1>[CH3:1][N:2]([CH3:6])[CH2:3][CH2:4][NH:5][S:17]([C:13]1[S:12][C:11]([NH:10][C:7](=[O:9])[CH3:8])=[N:15][C:14]=1[CH3:16])(=[O:18])=[O:19]
Reactant: CC(=O)Nc1nc(C)c(S(=O)(=O)Cl)s1
Reactant: CN(C)CCN
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)Nc1nc(C)c(S(=O)(=O)NCCN(C)C)s1
Temperature: 25 °C
Reaction time: 17 h
Yield: 88.9 %

Procedure:
To a stirred solution of N,N-dimethylethylenediamine (1.04 g, 11.8 mmol) in tetrahydrofurane (14 ml) was added at 0° C. (ice water bath) commercially available 2-acetamido-4-methylthiazole-5-sulfonyl chloride (1.0 g, 3.93 mmol) and triethylamine (0.6 ml, 4 mmol). The light yellow suspension was stirred at room temperature for 17 h, and evaporated. The crude product was further purified by column chromatography on silica gel (dichloromethane/MeOH/NH4OH 80:10:1) and subsequent crystallization (dichloromethane/hexane) to yield 2-acetamido-4-methyl-thiazole-5-sulfonic acid (2-dimethylamino-ethyl)-amide (1.07 g, 89%) as a white solid. MS (ISP) 305.1 [(M−H)−]; mp 143° C.
Reaction SMILES: [C:1]([O:4][CH2:5][CH3:6])(=[O:3])[CH3:2].O=[CH:8][C@@H:9]([C@H:11]([C@@H]([C@@H](CO)O)O)O)O>>[C:1]([O:4][CH2:5][CH2:6][CH:9]([CH3:11])[CH3:8])(=[O:3])[CH3:2]
Reactant: CCOC(C)=O
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Product: CC(=O)OCCC(C)C
Reaction time: 120 h

Procedure:
Liquid rich medium high in glucose content (10 ml PS-medium in 25 ml tube) was inoculated with the appropriate yeast strain and grown overnight at 30° C. 1-2 ml of this culture containing 107 cells was used to inoculate 50 ml fresh medium in a 250 ml conical flask. The culture was incubated at room temperature for 5 days with agitation (90 rpm.). Yeast cells were sedimented overnight at 4° C. and the supernatant discarded. 50 ml fresh medium was added to the cells and 2. generation fermentation performed as above. 25 ml supernatant from the fermentation was delivered for GC-headspace analysis (see below) to determine the content of esters and alcohols. The results are shown in Table 5.5. The yeast strains carrying inactive alcohol acetyltransferase genes produced a reduced amount of acetate esters such as ethyl acetate and isoamyl acetate in comparison to the MBP94-21 strain.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([S:19][CH3:20])=[CH:15][CH:14]=3)=[CH:11][C:10]([C:21]([OH:23])=O)=[N:9]2)=[CH:4][CH:3]=1.S(Cl)([Cl:26])=O>ClC(Cl)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([S:19][CH3:20])=[CH:15][CH:14]=3)=[CH:11][C:10]([C:21]([Cl:26])=[O:23])=[N:9]2)=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: CSc1ccc(-c2cc(C(=O)O)nn2-c2ccc(F)cc2)cc1
Solvent: CC(Cl)Cl
Product: CSc1ccc(-c2cc(C(=O)Cl)nn2-c2ccc(F)cc2)cc1

Procedure:
A mixture of 1-(4-fluorophenyl)-5-[4-(methylthio)phenyl]pyrazole-3-carboxylic acid (13.5 g) and thionyl chloride (10 ml) in dichloroethane (30 ml) was refluxed for 1 hour. The mixture was concentrated to give an oil of 1-(4-fluorophenyl)-5-[4-(methylthio)phenyl]pyrazole-3-carbonyl chloride.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:12])[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.S(=O)(O)[O-].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:12])[CH:10]=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C[C@@H](CO)NC(=O)OC(C)(C)C
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: C[C@@H](C=O)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 92 %

Procedure:
(S)-(−)-2-(tert-Butoxycarbonylamino)-1-propanol (523 mg, 2.98 mmol, 1.0 equiv.) was dissolved in 45 mL methylene chloride in a 100 mL r.b. flask with a magnetic stir bar. To this clear homogeneous solution, Dess-Martin periodinane (1.523 g, 3.591 mmol, 1.2 equiv.) was added in one portion and the cloudy white reaction mixture was allowed to stir at room temperature for 2 h. Thin-layer chromotography monitored the reaction to completion. The reaction mixture was diluted with 100 mL ethyl acetate. Sodium bisulfite solution (2 M, 20 mL) was added to the reaction mixture and the organic layer was separated. The aqueous layer was washed with 3×30 mL EtOAc. The combined organic layers were washed with 50 mL 1 M NaOH, followed by saturated NaCl (30 mL) and dried over MgSO4. Filtration and rotary evaporation produced the desired product as a yellow oil (475 mg, 92% yield, Rf=0.63, 1:1 hexanes/ethyl acetate).
Reaction SMILES: [CH3:1][C:2]1[N:10]([CH:11]([C:13](=[O:15])[CH3:14])[CH3:12])[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].[BH4-].[Na+].O>CO>[OH:15][CH:13]([CH3:14])[CH:11]([N:10]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[C:2]1[CH3:1])[CH3:12]
Reactant: CC(=O)C(C)n1c(C)c(C(=O)OC(C)(C)C)c2cccnc21
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Cc1c(C(=O)OC(C)(C)C)c2cccnc2n1C(C)C(C)O
Reaction time: 0.5 h
Yield: 96 %

Procedure:
To the solution of tert-butyl 2-methyl-1-(3-oxobutan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (3.1 g, 10.25 mmol) in methanol (30 mL) was added sodium borohydride (0.30 g, 8.2 mmol) at 0° C. After 30 minutes, another batch of sodium borohydride (0.30 g, 8.2 mmol) was added at 0° C. After the reaction completed about 2 h later, water (30 ml) was added dropwise very carefully to quench the reaction. The mixture was extracted with CH2Cl2. The extraction was dried over Na2SO4, filtered and concentrated under vacuum to give tert-butyl 1-(3-hydroxybutan-2-yl)-2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate as a yellow solid. (3.0 g, yield 96%) LCMS (M+H+) m/z: calcd 305.38. found 304.9. 1H NMR (400 MHz, CDCl3): ii 8.31-8.29 (m, 1H), 8.13-8.12 (m, 1H), 7.11-7.07 (m, 1H), 4.46-4.43 (m, 1H), 4.12 (m, 1H), 2.73 (s, 3H), 1.58 (s, 9H), 1.51-1.49 (d, 3H), 0.92-0.91 (d, 3H).
Reaction SMILES: [CH:1]1([NH:7][C:8]([C:10]2[C:11](=O)[C:12]3[C:17]([C:18]=2[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:16][CH:15]=[C:14]([O:25][CH2:26][CH2:27][N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH:13]=3)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH2:36][OH:37].N1C=CC=CC=1>C(O)C>[CH:1]1([NH:7][C:8]([C:10]2[C:11](=[N:36][OH:37])[C:12]3[C:17]([C:18]=2[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:16][CH:15]=[C:14]([O:25][CH2:26][CH2:27][N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH:13]=3)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=C(NC1CCCCC1)C1=C(c2ccccc2)c2ccc(OCCN3CCOCC3)cc2C1=O
Reactant: NO
Agent: Cl
Solvent: CCO
Solvent: c1ccncc1
Product: O=C(NC1CCCCC1)C1=C(c2ccccc2)c2ccc(OCCN3CCOCC3)cc2C1=NO
Temperature: 25 °C
Yield: 64.1 %

Procedure:
6-(2-Morpholine-4-ylethoxy)-1-oxo-3-phenyl-1H-indene-2-carboxylic acid cyclohexylamide (130 mg, 0.28%) obtained in Step 4 was dissolved in ethanol (20 mL), and hydroxylamine hydrochloride (60 mg, 0.85 mmol) and pyridine (892 mg, 1.13 mmol) were added thereto. The mixture was refluxed for 1 hr, and cooled to RT, and extracted with dichloromethane. The organic layer was separated, dried over anhydrous MgSO4 and concentrated under a reduced pressure. The resulting residue was purified by flash chromatography to obtain 86 mg of 1-hydroxyimino-6-(2-morpholine-4-yl-ethoxy)-3-phenyl-1H-indene-2-carboxylic acid cyclohexylamide (yield: 64%). Subsequently, 1-hydroxyimino-6-(2-morpholine-4-yl-ethoxy)-3-phenyl-1H-indene-2-carboxylic acid cyclohexylamide (80 mg, 0.17 mmol) thus obtained was dissolved in methanol (20 mL) and 10%-palladium (100 mg) was added thereto. The mixture was stirred for 15 hrs at RT while providing H2 gas thereto using a balloon, filtered through celite, and concentrated under a reduced pressure. Then, the resulting residue was purified by flash chromatography to obtain 14 mg of the titled compound (yield: 18%).
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([OH:12])=O)=[CH:9][C:4]=2[NH:3][CH:2]=1.[CH3:13][N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1>>[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:10]([C:8]2[CH:7]=[CH:6][C:5]3[NH:1][CH:2]=[N:3][C:4]=3[CH:9]=2)=[O:12])[CH2:16][CH2:15]1
Reactant: CN1CCNCC1
Reactant: O=C(O)c1ccc2nc[nH]c2c1
Product: CN1CCN(C(=O)c2ccc3[nH]cnc3c2)CC1
Yield: 62.2 %

Procedure:
In a procedure analogous to example 20, reaction of benzimidazole-5-carboxylic acid (400 mg, 2.50 mmol) and N-methylpiperazine (550 mg, 5.0 mmol) furnished the product (380 mg, 63%).
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[CH2:3][O:4][C:5](=[NH:14])[C:6]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[NH:7].C([Li])CCC.CCCCCC.[C:28]1([Sb:34](Cl)Cl)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CCOCC>[C:28]1([Sb:34]2[N:14]=[C:5]([O:4][CH2:3][C:2]([F:15])([F:16])[F:1])[C:6]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[N:7]2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: Cl[Sb](Cl)c1ccccc1
Reactant: N=C(OCC(F)(F)F)C(=N)OCC(F)(F)F
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Product: FC(F)(F)COC1=N[Sb](c2ccccc2)N=C1OCC(F)(F)F
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 45 %

Procedure:
The compound 1,2-di(2,2,2-trifluoroethoxy)ethanediimine (1.2 g, 5 mmol) was placed into a 50 mL Schlenk flask and the flask was flushed with nitrogen. Approximately 20 mL anhydrous diethyl ether was added, and the solution was cooled to approximately -70° to -80° C. (dry ice/isopropanol). Ten mmol (4.9 mL, 2.03M) n-butyllithium/hexane was then added dropwise via syringe; the solution was stirred at -78° C. for approximately 30 minutes. A solution of 1.35 g (5.0 mmol) of phenylantimony dichloride [(C6H5)SbCl2 ] in 25 mL of ether was then added dropwise via syringe. The reaction mixture was allowed to warm to room temperature while stirring. After stirring at room temperature for approximately 1-2 hours, the mixture was filtered through a fritted funnel, and the filtrate evaporated in vacuo. The solid residue was sublimed (1 torr, room temperature) to yield the white crystalline product 2-phenyl-4,5-di(2,2,2-trifluoroethoxy)-1,3,2-diazastibole in 45% yield (1.01 g, 2.25 mmol). 13C[1H]NMR (δ; CD2Cl2) 156.0 ppm (>C=N--; s), 152.2, 132.2, 131.5, and 129.3 ppm (phenyl C), 124.8 ppm (--CF3, t, J1 =278.0 Hz), 63.7 ppm (q, J2 =34.9Hz). Elemental analysis was carried out: calcd (found) for C12H9N2O2F6Sb: C, 32.10% (32.17%), H, 2.02% (2.09%), N, 6.24% (6.31%), F, 25.39% (25.43%), Sb 27.12% (27.20%).
Reaction SMILES: FC(F)(F)COP([CH2:13][C:14]([O:16][CH3:17])=[O:15])(OCC(F)(F)F)=O.C1OCCOCCOCCOCCOCCOC1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:48][C:49]1[CH:56]=[CH:55][C:52]([CH:53]=O)=[CH:51][CH:50]=1>C1COCC1.[Cl-].[NH4+]>[F:48][C:49]1[CH:56]=[CH:55][C:52](/[CH:53]=[CH:13]\[C:14]([O:16][CH3:17])=[O:15])=[CH:51][CH:50]=1
Reactant: COC(=O)CP(=O)(OCC(F)(F)F)OCC(F)(F)F
Reactant: O=Cc1ccc(F)cc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Solvent: C1CCOC1
Product: COC(=O)/C=C\c1ccc(F)cc1
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 79.1 %

Procedure:
To a solution of methyl [bis(2,2,2-trifluoroethoxy)phosphoryl]acetate (5.0 g) and 18-crown-6 (10.3 g) in THF (200 mL) was added dropwise at −78° C. potassium bis(trimethylsilyl)amide (15% toluene solution, 21 mL), and 4-fluorobenzaldehyde (1.95 g) was added. The reaction mixture was stirred at −78° C. for 20 min, and the mixture was stirred at room temperature for 1 hr. The mixture was diluted with saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The extract was washed with saturated brine, dried and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (solvent gradient; 5→15% ethyl acetate/hexane) to give methyl (2Z)-3-(4-fluorophenyl)prop-2-enoate (2.24 g, 79%) as a colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[C:20]([CH:24]([CH3:28])[C:25](O)=[O:26])[CH:21]=[CH:22][CH:23]=3)[CH:16]=2)[N:11]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[N:10]=1.[CH3:37][NH:38][CH3:39].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[C:20]([CH:24]([CH3:28])[C:25]([N:38]([CH3:39])[CH3:37])=[O:26])[CH:21]=[CH:22][CH:23]=3)[CH:16]=2)[N:11]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:34])([CH3:35])[CH3:36])[N:10]=1
Reactant: COc1ccccc1-c1nn(COCC[Si](C)(C)C)c2ncc(-c3cccc(C(C)C(=O)O)c3)cc12
Reactant: CNC
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccccc1-c1nn(COCC[Si](C)(C)C)c2ncc(-c3cccc(C(C)C(=O)N(C)C)c3)cc12
Temperature: 60 °C

Procedure:
To a solution of 2-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-propionic acid, (100 mg, 0.20 mmol), dimethylamine (2 N in THF, 0.143 mL, 0.29 mmol), and diisopropylethylamine (37 mg, 0.29 mmol) in THF (2 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (110 mg, 0.29 mmol.). The resulting suspension was heated to 60° C. with stirring until all was dissolved. The solvent was evaporated and the residue was used in next step without purification. MS: m/z 547 (M+H+).
Reaction SMILES: C(N(CC)CC)C.Cl.[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:12][CH:11]=1.[I-].C[N+]1C=CC=CC=1Cl.[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([S:38]([NH:41][CH:42]([CH2:46][CH3:47])[C:43](O)=[O:44])(=[O:40])=[O:39])=[CH:34][CH:33]=1>C(Cl)(Cl)Cl>[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([S:38]([NH:41][CH:42]([CH2:46][CH3:47])[C:43]([NH:9][C:10]2[CH:11]=[CH:12][C:13]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:14][CH:15]=2)=[O:44])(=[O:39])=[O:40])=[CH:36][CH:37]=1
Reactant: CCOC(=O)Cc1ccc(N)cc1
Reactant: CCC(NS(=O)(=O)c1ccc(Cl)cc1)C(=O)O
Agent: C[n+]1ccccc1Cl
Agent: Cl
Agent: [I-]
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CCOC(=O)Cc1ccc(NC(=O)C(CC)NS(=O)(=O)c2ccc(Cl)cc2)cc1
Yield: 16.7 %

Procedure:
Triethylamine (1.99 ml), ethyl 4-aminophenylacetate hydrochloride (699 mg), and 1-methyl-2-chloropyridinium iodide (1.1 g) were added to a solution of (RS)-2-(4-chlorobenzenesulfonylamino)butanoic acid (1 g) in chloroform (30 ml), and the whole was heated under reflux for 2 hours under argon. The reaction mixture was concentrated under reduced pressure. After adding 1N HCl, the residue was extracted with ethyl acetate. The combined ethyl acetate layers were washed with a saturated saline solution, and dried over Na2SO4. The solvent was evaporated under reduced pressure. The residue was purified by column chromatography (silica gel 70 g, hexane/ethyl acetate=2/1) to give (RS)-2-(4-chlorobenzenesulfonylamino)-N-(4-(ethoxycarbonylmethyl) phenyl)butanamide (237 mg).
Reaction SMILES: C([Li])(C)(C)C.Br[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[C:9]([F:14])[CH:8]=1.CN(C)[CH:17]=[O:18].S(=O)(=O)(O)[O-].[K+]>C1(C)C=CC=CC=1.O1CCCC1>[F:14][C:9]1[CH:8]=[C:7]([CH:12]=[CH:11][C:10]=1[CH3:13])[CH:17]=[O:18]
Reactant: Cc1ccc(Br)cc1F
Reactant: CN(C)C=O
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: Cc1ccc(C=O)cc1F
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 91.9 %

Procedure:
tert-Butyllithium (31 ml of a 1.7 M solution in toluene, 52 mmol) was added slowly over 30 minutes to a cold (−70° C.), stirred solution of 4-bromo-2-fluorotoluene (5 g, 26 mmol) in tetrahydrofuran (25 ml). After addition was complete, the mixture was stirred for 15 minutes and a solution of dimethylformamide (2 g, 28 mmol) in tetrahydrofuran (10 ml) was then added over 10 minutes. After addition was complete, the reaction solution was warmed to room temperature over 30 minutes. The reaction was poured into 0.5N aqueous potassium bisulfate (125 ml) and extracted with ethyl ether. The combined organic extracts were dried over sodium sulfate and evaporated to give 3.3 g (90%) of the desired product as an oil. This material was suitable for use without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])(=[O:12])=[O:11])[CH2:7][N:6]1[C:23](=S)[CH2:24][C:25](=O)[CH3:26])=[O:4].[CH3:29][NH:30][NH2:31]>>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])(=[O:12])=[O:11])[CH2:7][N:6]1[C:23]1[CH:24]=[C:25]([CH3:26])[N:30]([CH3:29])[N:31]=1)=[O:4]
Reactant: COC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2C(F)(F)F)CN1C(=S)CC(C)=O
Reactant: CNN
Product: COC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2C(F)(F)F)CN1c1cc(C)n(C)n1

Procedure:
In analogy to the procedure described in example 192 h, (2S,4R)-1-(3-oxo-thiobutyryl)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid methyl ester (example 192 g) was reacted with methyl-hydrazine (CAS Reg. No. 60-34-4) to give the title compound as yellow solid. MS (ESI): m/z=432.1 [M+H]+.