Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C@@H:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4].C([Sn](=O)CCCC)CCC.[CH:29]1[CH:34]=[CH:33][C:32]([CH2:35]Br)=[CH:31][CH:30]=1>CO.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-]>[CH2:35]([O:6][C@H:5]1[C@@H:7]([OH:8])[C@@H:9]([CH2:11][OH:12])[O:10][C@@H:2]([S:1][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C@@H:3]1[OH:4])[C:32]1[CH:33]=[CH:34][CH:29]=[CH:30][CH:31]=1
Reactant: BrCc1ccccc1
Reactant: OC[C@H]1O[C@@H](Sc2ccccc2)[C@H](O)[C@@H](O)[C@H]1O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: CCCC[Sn](=O)CCCC
Agent: [Br-]
Solvent: CO
Product: OC[C@H]1O[C@@H](Sc2ccccc2)[C@H](O)[C@@H](OCc2ccccc2)[C@H]1O
Temperature: 25 °C
Yield: 68 %

Procedure:
A solution of phenyl 1-thio-β-D-galactopyranoside (2.1) (3.00 g, 11.0 mmol) and dibutyltin oxide (3.00 g, 12.1 mmol) in dry methanol (80 ml) was refluxed for 2 hours to produce a clear mixture. The solvent was then evaporated under reduced pressure. The resultant residue was dissolved in dry benzene (80 mL) followed by the addition of Bu4NBr (3.90 g, 12.11 mmol) and BnBr (1.3 ml, 12.1 mmol). The mixture was refluxed overnight. After cooling to room temperature, the mixture was concentrated and the residue was purified by silica gel chromatography (50% EtOAc/petroleum ether) to afford the title compound (2.71 g, 7.48 mmol, 67%). 1H NMR (400 MHz, CDCl3): δ 7.60-7.20 (m, 10H, PhH), 4.77, 4.68 (ABq, J=11.7 Hz, 1H each, OCH2Ph), 4.59 (d, J=9.5 Hz, 1H, H-1), 4.08 (d, J=2.6 Hz, 1H, H-4), 3.76 (dd, J=9.5, 9.5 Hz, 1H, H-2), 3.75 (dd, J=11.4, 5.8 Hz, 1H, H-6), 3.70 (dd, J=11.4, 5.8 Hz, 1H, H-6), 3.50 (dd, J=5.8, 5.8 Hz, 1H, H-5), 3.41 (dd, J=9.5, 2.6 Hz, 1H, H-3); 13C NMR (100 MHz, CDCl3): δ 131.0, 128.6, 128.1, 127.8, 127.4, 126.8, 89.1, 82.5, 79.2, 71.5, 69.0, 66.2, 61.4; HRMS calcd for C19H26O5SN [M+NH4]+: 380.1532. found 380.1527.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:8]2([OH:28])[CH2:13][CH2:12][N:11]([C:14]3[N:15]=[N:16][C:17]([O:20]CC4C=CC=CC=4)=[CH:18][CH:19]=3)[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[H][H]>[Pd].COCCO>[OH:28][C:8]1([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=2)[CH2:9][CH2:10][N:11]([C:14]2[N:15]=[N:16][C:17]([OH:20])=[CH:18][CH:19]=2)[CH2:12][CH2:13]1
Reactant: Cc1cccc(C2(O)CCN(c3ccc(OCc4ccccc4)nn3)CC2)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: COCCO
Product: Cc1cccc(C2(O)CCN(c3ccc(O)nn3)CC2)c1
Yield: 97 %

Procedure:
A mixture of 6.1 parts of 4-(3-methylphenyl)-1-[6-(phenylmethoxy)-3-pyridazinyl]-4-piperidinol and 250 parts of 2-methoxyethanol was hydrogenated at normal pressure and at room temperature with 2 parts of palladium-on-charcoal catalyst 10%. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated. The residue was boiled in 2-propanol. The product was filtered off and dried, yielding 4.5 parts (97%) of 6-[4-hydroxy-4-(3-methylphenyl)-1-piperidinyl)-3-pyridazinol; mp. 264.6° C. (compound 269).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]=[CH2:15])[CH2:10][CH2:9]1)=O)(C)(C)C.C12BC(CCC1)CCC2.Br[C:26]1[C:27]2[N:34]([CH2:35][CH3:36])[C:33]([C:37]3[C:38]([NH2:42])=[N:39][O:40][N:41]=3)=[N:32][C:28]=2[CH:29]=[N:30][CH:31]=1.[OH-].[Na+]>O1CCCC1.ClCCl>[CH2:35]([N:34]1[C:27]2[C:26]([CH2:15][CH2:14][CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[CH:31][N:30]=[CH:29][C:28]=2[N:32]=[C:33]1[C:37]1[C:38]([NH2:42])=[N:39][O:40][N:41]=1)[CH3:36]
Reactant: CCn1c(-c2nonc2N)nc2cncc(Br)c21
Reactant: C=CC1CCN(C(=O)OC(C)(C)C)CC1
Agent: B1C2CCCC1CCC2
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCn1c(-c2nonc2N)nc2cncc(CCC3CCNCC3)c21
Temperature: 25 °C
Reaction time: 6 h
Yield: 6.7 %

Procedure:
A solution of 4-vinyl-piperidine-1-carboxylic acid tert-butyl ester (WO 9620192) (1.2 mM: 252 mg) in dry tetrahydrofuran (4 ml) was treated with a 0.5M solution of 9-borabicyclo[3.3.1]-nonane in tetrahydrofuran (1.2 mM; 2.4 ml) and stirred at room temperature for 6 hours under argon. The mixture was treated with the product of Example 100 (1.0 mM; 309 mg), 1,1′-bis(diphenylphosphino)ferrocene dichloro palladium(II) complex with dichloromethane (25 mg) and a 3M aqueous solution of sodium hydroxide (1 ml). The resulting mixture was heated at reflux under argon for 18 hours and purified on a 5 g SCX ion exchange cartridge. After removal of the solvent in vacuo the resulting yellow gum was treated with trifluoroacetic acid at room temperature for 2 hours and the solution passed through a 5 g SCX ion exchange cartridge. The solvent was removed in vacuo and the residue purified on a 5 g silica solid phase extraction cartridge eluting with 1-5-94 ammonia-methanol-dichloromethane to give the title compound as a white solid (23 mg). MS (ES+) m/e 342 [M+H]+.
Reaction SMILES: [C:1]([NH:8][C@@H:9]([C:12]([OH:14])=[O:13])[CH2:10][OH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C)([O-])C.[K+].[F:21][C:22]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:23]=1[CH2:24]Br>C1COCC1.CN(C=O)C>[C:4]([O:3][C:1]([NH:8][CH:9]([CH2:10][O:11][CH2:24][C:23]1[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:22]=1[F:21])[C:12]([OH:14])=[O:13])=[O:2])([CH3:7])([CH3:6])[CH3:5]
Reactant: CC(C)(C)OC(=O)N[C@H](CO)C(=O)O
Reactant: Fc1ccc(CBr)c(F)c1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NC(COCc1ccc(F)cc1F)C(=O)O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 71 %

Procedure:
To a solution of N-Boc-(D)-serine (452 g, 2.2026 mol) in a mixture of THF (7 L) and DMF (3 L) at about 0° C. was added potassium tert-butoxide solution (515.8 g, 4.5963 mol). The reaction mixture was stirred at about 0° C. for about 30 min., then 2.4-difluorobenzyl bromide (456.5 g, 2.2051 mol) was added. After warming to room temperature, the reaction mixture was concentrated in vacuo to remove the THF. The reaction mixture was partitioned between 4.5 L H2O and 4.5 L IPE. The layers were saparated and the pH of the aqueous layer was adjusted with 1 N HCl to about 3. The aqueous layer was extracted twice with 4 L each of IPE. The organic solution was dried over Na2SO4, and concentrated in vacuo to yield a yellow waxy solid (518.0 g, yield: 70.9%). 1H-NMR (CDCl3) δ 1.44 (s, 9H), 0.73 (m, 1H), 3.94 (d, 1H). 4.44 (br s, 1H), 4.54 (s, 2H), 5.34 (m, 1H), 6.78 (m, 1H), 0.84 (m, 1H), 7.30 (m, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)([C:13]#[N:14])[CH:11]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[NH:10][CH:9]2[C:27]([OH:29])=O)[CH:5]=[CH:6][CH:7]=1.[N:30]1([CH2:36][CH2:37][NH2:38])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C>C(Cl)Cl>[N:30]1([CH2:36][CH2:37][NH:38][C:27]([CH:9]2[CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[C:12]([C:15]3[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=3)([C:13]#[N:14])[CH:11]([CH2:22][C:23]([CH3:26])([CH3:24])[CH3:25])[NH:10]2)=[O:29])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1
Reactant: NCCN1CCOCC1
Reactant: CC(C)(C)CC1NC(C(=O)O)C(c2cccc(Cl)c2)C1(C#N)c1ccc(Cl)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)CC1NC(C(=O)NCCN2CCOCC2)C(c2cccc(Cl)c2)C1(C#N)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.5 %

Procedure:
A mixture of rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (61.0 mg, 0.14 mmol), 2-morpholin-4-yl-ethylamine (36.0 mg, 0.28 mmol), 2-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 106.0 mg, 0.28 mmol) and iPr2NEt (38.8 mg, 0.30 mmol) in CH2Cl2 (2 mL) was stirred at rt overnight. The mixture was then diluted with CH2Cl2 and washed with water, brine. The organic phase was separated, filtered and dried over Na2SO4. The mixture was then concentrated and purified by SiO2 flash column (20-100% of EtOAc in Hexanes) to give rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (2-morpholin-4-yl-ethyl)-amide (60.5 mg, 86.4%) as a white amorphous.
Reaction SMILES: CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH:18]=[CH:17][C:16]([OH:19])=[N:15]2)=[CH:10][CH:9]=1.Cl[C:21]1[C:26]([C:27](=[O:32])[C:28]([O:30][CH3:31])=[O:29])=[CH:25][CH:24]=[CH:23][N:22]=1.Cl>C(O)(C)(C)C.CS(C)=O>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([N:14]2[CH:18]=[CH:17][C:16]([O:19][C:21]3[C:26]([C:27](=[O:32])[C:28]([O:30][CH3:31])=[O:29])=[CH:25][CH:24]=[CH:23][N:22]=3)=[N:15]2)=[CH:12][CH:13]=1
Reactant: Oc1ccn(-c2ccc(Cl)cc2)n1
Reactant: COC(=O)C(=O)c1cccnc1Cl
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CS(C)=O
Solvent: CC(C)(C)O
Product: COC(=O)C(=O)c1cccnc1Oc1ccn(-c2ccc(Cl)cc2)n1
Reaction time: 1 h
Yield: 40.4 %

Procedure:
At 60° C., 4.7 g (42 mmol) of potassium tert-butoxide were added a little at a time to a solution of 7.4 g (38.1 mmol) of 1-(4-chlorophenyl)-3-hydroxypyrazole in 15 ml of tert-butanol. The mixture was stirred at this temperature for 1 hour and the solvent was then removed under reduced pressure. The residue was dissolved in 25 ml of abs. dimethyl sulfoxide, and a solution of 8.0 g (38.1 mmol) of methyl (2-chloropyridin-3-yl)glyoxylate in 10 ml of abs. dimethyl sulfoxide was then added at such a rate that the temperature did not exceed 30° C. After 30 minutes at room temperature, 50 ml of 0.5 N HCl were added and the reaction mixture was extracted repeatedly with ethyl acetate. The combined organic phases were washed with water and dried over sodium sulfate. The solvent was subsequently removed under reduced pressure. The resulting residue was purified by silica gel column chromatography using cyclohexane/ethyl acetate (10:1) as eluant. 5.5 g (40%) of the title compound were obtained as a clear oil.
Reaction SMILES: C(OC([NH:8][C:9]([CH3:21])([CH3:20])[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=O)(C)(C)C.[ClH:22]>C(OCC)C>[ClH:22].[NH2:8][C:9]([CH3:21])([CH3:20])[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11]
Reactant: CC(C)(C)OC(=O)NC(C)(C)C(=O)OCc1ccccc1
Agent: Cl
Solvent: CCOCC
Product: CC(C)(N)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2-(tert-butoxycarbonylamino)-2-methylpropionic acid (4.06 g) in N,N-dimethylformamide (40 mL) were added potassium carbonate (4.15 g) and benzyl bromide (2.85 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethylacetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue (solid) was treated with n-hexane and collected by filtration. The crystals were dried under reduced pressure to give benzyl 2-(tert-butoxycarbonylamino)-2-methylpropionate (4.44 g). To the obtained benzyl 2-(tert-butoxycarbonylamino)-2-methylpropionate (4.44 g) was added 4 mol/L hydrochloric acid (1,4-dioxane solution, 15 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with diethyl ether, and the mixture was stirred for 1 hour. The insoluble material was collected by filtration, washed with diethyl ether and dried under reduced pressure to give the title compound (3.4 g).
Reaction SMILES: [SH:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:14][C:15]1[C:24]2[C:19](=[C:20]([NH:25][C:26](=[O:35])[C:27]3[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])[CH:21]=[CH:22][CH:23]=2)[N:18]=[CH:17][C:16]=1[C:36]([O:38][CH2:39][CH3:40])=[O:37].O>CN(C)C=O>[Cl:34][C:28]1[CH:29]=[CH:30][CH:31]=[C:32]([Cl:33])[C:27]=1[C:26]([NH:25][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:19]=1[N:18]=[CH:17][C:16]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[C:15]2[CH2:14][S:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1)=[O:35]
Reactant: Sc1ncc[nH]1
Reactant: CCOC(=O)c1cnc2c(NC(=O)c3c(Cl)cccc3Cl)cccc2c1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1cnc2c(NC(=O)c3c(Cl)cccc3Cl)cccc2c1CSc1ncc[nH]1
Reaction time: 0.25 h
Yield: 92.2 %

Procedure:
To a solution of 2-mercaptoimidazole (27.4 mg) in dimethylformamide (1.5 ml) was added potassium carbonate (51.6 mg) under ice-cooling, and the mixture was stirred for 15 minutes at the same temperature. To the mixture was added 4-bromomethyl-8-(2,6-dichlorobenzoylamino)-3-ethoxycarbonylquinoline (120 mg) under ice-cooling, and the mixture was stirred for 1 hour at ambient temperature. To the mixture was added water under ice-cooling, and the resulting precipitate was collected by filtration and washed with water to give 8-(2,6-dichlorobenzoylamino)-3-ethoxycarbonyl-4-[(imidazol-2-yl)thiomethyl]quinoline (115 mg).
Reaction SMILES: [NH2:1][C:2]1[C:7]([S:8]([NH:11][C@H:12]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13]2)(=[O:10])=[O:9])=[CH:6][C:5](Br)=[CH:4][N:3]=1.[CH3:19][C:20]1[N:29]=[C:28]([N:30]2[CH2:36][C:35]3[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][C:34]=3[O:33][CH2:32][CH2:31]2)[C:27]2[CH2:26][C:25]([CH3:45])([CH3:44])[CH2:24][CH2:23][C:22]=2[N:21]=1>>[NH2:1][C:2]1[C:7]([S:8]([NH:11][C@@H:12]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13]2)(=[O:10])=[O:9])=[CH:6][C:5]([C:38]2[CH:39]=[CH:40][C:34]3[O:33][CH2:32][CH2:31][N:30]([C:28]4[C:27]5[CH2:26][C:25]([CH3:44])([CH3:45])[CH2:24][CH2:23][C:22]=5[N:21]=[C:20]([CH3:19])[N:29]=4)[CH2:36][C:35]=3[CH:37]=2)=[CH:4][N:3]=1
Reactant: Cc1nc2c(c(N3CCOc4ccc(B(O)O)cc4C3)n1)CC(C)(C)CC2
Reactant: CN1CC[C@H](NS(=O)(=O)c2cc(Br)cnc2N)C1
Product: Cc1nc2c(c(N3CCOc4ccc(-c5cnc(N)c(S(=O)(=O)N[C@@H]6CCN(C)C6)c5)cc4C3)n1)CC(C)(C)CC2

Procedure:
Synthesized according to the method of example 5 using (S)-2-amino-5-bromo-N-(1-methylpyrrolidin-3-yl)pyridine-3-sulfonamide (reagent preparation 25) and [4-(2,6,6-trimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]boronic acid (reagent preparation 23) in step 1. 1H NMR (400 MHz, d6-DMSO): 8.52 (d, 1H), 8.07 (d, 1H), 7.61 (d, 1H), 7.45 (dd, 1H), 7.02 (d, 1H), 6.68 (br s, 2H), 4.57 (s, 2H), 4.25 (br t, 2H), 3.82 (br m, 2H), 3.63 (br m, 1H), 2.65 (t, 2H), 2.43 (m, 4H), 2.33 (s, 3H), 2.22 (br m, 2H), 2.13 (s, 3H), 1.84 (s, 5H), 1.57 (t, 2H), 1.45 (m, 1H), 0.83 (s, 6H); MS (EI) for C30H39N7O3S: 578 (MH+).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([N:10]([CH2:23][CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][CH:29]([CH2:32][C:33]3[CH:38]=[CH:37][C:36]([C:39]4[N:40]=[N:41][N:42](C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[N:43]=4)=[CH:35][CH:34]=3)[CH2:28][CH2:27]2)[C:11]([CH:13]2[CH2:18][CH2:17][N:16]([S:19]([CH3:22])(=[O:21])=[O:20])[CH2:15][CH2:14]2)=[O:12])[CH:6]=[CH:7][C:8]=1[Cl:9]>C(OCC)(=O)C.C(OCC)(=O)C.CO>[ClH:2].[Cl:2][C:3]1[CH:4]=[C:5]([N:10]([CH2:23][CH2:24][CH2:25][N:26]2[CH2:27][CH2:28][CH:29]([CH2:32][C:33]3[CH:34]=[CH:35][C:36]([C:39]4[N:40]=[N:41][NH:42][N:43]=4)=[CH:37][CH:38]=3)[CH2:30][CH2:31]2)[C:11]([CH:13]2[CH2:14][CH2:15][N:16]([S:19]([CH3:22])(=[O:20])=[O:21])[CH2:17][CH2:18]2)=[O:12])[CH:6]=[CH:7][C:8]=1[Cl:9]
Reactant: CS(=O)(=O)N1CCC(C(=O)N(CCCN2CCC(Cc3ccc(-c4nnn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc3)CC2)c2ccc(Cl)c(Cl)c2)CC1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CO
Product: CS(=O)(=O)N1CCC(C(=O)N(CCCN2CCC(Cc3ccc(-c4nn[nH]n4)cc3)CC2)c2ccc(Cl)c(Cl)c2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 194.7 %

Procedure:
A solution of 4N hydrogen chloride in ethyl acetate (15 ml) was to a solution of the title compound of example 357 (263 mg, 0.3 mmol) in ethyl acetate-methanol (2/5, 7 ml) and this solution was stirred at room temperature for 1 h. The resulting mixture was concentrated in vacuo. The residue was crystallized from methanol-ethyl acetate (1/1) to give the title compound (196 mg, 97%) as colorless crystalline powder.
Reaction SMILES: [NH2:1][C:2]1[C:3]([CH3:8])=[CH:4][CH:5]=[CH:6][CH:7]=1.N1C=CC=CC=1.[CH3:15][S:16](Cl)(=[O:18])=[O:17]>ClCCl>[CH3:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][S:16]([CH3:15])(=[O:18])=[O:17]
Reactant: CS(=O)(=O)Cl
Reactant: Cc1ccccc1N
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1ccccc1NS(C)(=O)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
To a solution of o-toluidine (1.07 ml, 10 mmol) and pyridine (0.86 ml, 10.6 mmol) in dichloromethane (2 mL) was added methanesulfonyl chloride (0.81 ml, 10.5 mmol) dropwise at 0° C. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched by 1 N HCl aqueous solution and extracted with EtOAc. The organic layer was concentrated in vacuo to afford the title compound (1.84 g, 10 mmol, quant.) as an orange solid.
Reaction SMILES: [C:1]([O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)(=[O:5])[C@H:2]([CH3:4])[OH:3].C(N(CC)CC)C.C(Cl)Cl.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25].Cl>>[C:23]([O:3][C@@H:2]([CH3:4])[C:1]([O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:5])(=[O:26])[CH:24]=[CH2:25]
Reactant: C[C@H](O)C(=O)OC1CCCCC1
Reactant: C=CC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=CC(=O)O[C@@H](C)C(=O)OC1CCCCC1
Temperature: -20 °C
Reaction time: 5.5 h
Yield: 102 %

Procedure:
To a mixture of 10.1 g (58.5 mmol) of cyclohexyl (s)-(-)-lactate, 8.1 g (80.4 mmol) of triethylamine and ml of methylene chloride, 5.7 ml (70.2 mmol) of acryloyl chloride was added dropwise at a temperature of -20° C., and the mixture was stirred at -20° C. for 5.5 hours. On ice cooling, 1N hydrochloric acid was added to the reaction mixture to separate an organic layer, and an aqueous layer was extracted with methylene chloride. Organic layers were combined and washed with successive, saturated sodium bicarbonate solution, water, and saturated sodium chloride solution. The solution was dried over anhydrous magnesium sulfate and filtered, the solvent was distilled off, and 13.5 g of crude (S)-cyclohexyl 2-propenoyloxypropionate was obtained.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH2:13][C:14](OCC)=[O:15])[CH:10]=[CH:11][CH:12]=2)[N:5]=[C:4]([C:19]([F:22])([F:21])[F:20])[CH:3]=1.[NH4+:23].[OH-]>>[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH2:13][C:14]([NH2:23])=[O:15])[CH:10]=[CH:11][CH:12]=2)[N:5]=[C:4]([C:19]([F:22])([F:21])[F:20])[CH:3]=1
Reactant: [NH4+]
Reactant: CCOC(=O)Cc1cccc(-n2nc(C(F)(F)F)cc2N)c1
Agent: [OH-]
Product: NC(=O)Cc1cccc(-n2nc(C(F)(F)F)cc2N)c1
Yield: 66 %

Procedure:
A solution of ethyl 2-(3-(5-amino-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)acetate (3 g, 9.58 mmol) in conc. NH4OH (40 mL) was heated at reflux for 2 h. After removal of the solvent, the residue was purified by column chromatography to afford 2-(3-(5-amino-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)acetamide (1.8 mg, 66% yield). 1H NMR (300 MHz, DMSO-d6): 7.48-7.42 (m, 4H), 7.30 (s, 1H), 6.91 (s, 1H), 5.77 (s, 1H), 5.73-5.72 (m, 2H), 4.44 (s, 2H). MS (ESI) m/z: 285 (M+H+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5](O)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].S(Cl)([Cl:14])=O>CN(C)C=O>[Br:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=[O:8])[C:5]([Cl:14])=[N:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1cc(Br)cnc1O
Solvent: CN(C)C=O
Product: O=C(O)c1cc(Br)cnc1Cl

Procedure:
To 15 g (0.069 mole) of 5-bromo-2-hydroxy nicotinic acid was added 75 ml of thionyl chloride and 3 ml of dimethylformamide. The mixture was heated to reflux for 30 minutes. After cooling, the excess thionyl chloride was removed by rotary evaporation and the residue poured into water (1 liter) with vigorous agitation. The precipitate was collected and the mother liquor condensed to 1/2 the volume, yielding additional precipitate. The precipitates were combined and crystallized from toluene giving 6 g (37%) of material. The product was recrystallized from toluene, m.p. 174°-177° C.
Reaction SMILES: [F:1][C:2]1[C:3](Br)=[C:4](Br)[CH:5]=[CH:6][C:7]=1[F:8].[O:11]1[CH:15]=[CH:14][CH:13]=[CH:12]1.[Li]CCCC>CCOCC>[F:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][C:7]=1[F:8])[CH:15]1[O:11][CH:12]2[CH:13]=[CH:14]1
Reactant: Fc1ccc(Br)c(Br)c1F
Reactant: c1ccoc1
Agent: [Li]CCCC
Solvent: CCOCC
Product: Fc1cc2c(cc1F)C1C=CC2O1
Temperature: -78 °C
Reaction time: 2 h
Yield: 69.9 %

Procedure:
To 3,4-difluoro-1,2-dibromo-benzene (0.75 g, 2.78 mmol) and furan (1 mL, 14.7 mmol) in Et2O (15 mL) at −78° C. was added BuLi (1.1 mL, 2.5M in hexanes, 2.75 mmol) dropwise. The reaction was stirred for two hours at −78° C. and then was allowed to warm to room temperature. After 2 hours, the reaction mixture was quenched with water dropwise and then was poured into water. The organic layer was separated and the aqueous layer was extracted three times with Et2O. The combined organic layers were washed with brine, dried over MgSO4, concentrated and chromatographed (25% ethyl acetate:hexanes) on silica gel to give 24 (350 mg, 70%) as a colourless oil. Rf=0.21 on silica gel (20% ethyl acetate:hexanes); bp 40° C. @ 0.5 mmHg]; IR (neat, cm−1), 3017 (M), 1624 (s), 1465 (s), 1365 (s), 1253 (s), 1190 (m), 1040 (s), 857 (s). 1H NMR (400 MHz, CDCl3) δ7.06 (2H, dd, JH-F=7.7, 7.7 Hz), 7.01 (2H, s), 5.67 (2H, s); 13C NMR (400 MHz, CDCl3) δ147.2 (dd, JC-F=247.9, 14.5 Hz), 145.1 (dd, JC-F=4.3, 4.3 Hz), 143.1, 110.8 (m), 82.1. HRMS calcd for C10H6O (M+): 180.0387. Found: 180.0394.
Reaction SMILES: ClCCl.[N:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]3[CH2:12][NH:13][C:14](=[O:26])[C:15]=3[CH:16]=[C:17]3[CH:25]=[CH:24][C:23]4[O:22][CH2:21][O:20][C:19]=4[C:18]=23)=[CH:6][CH:5]=1.C1C=C(Cl)C=C(C(OO)=[O:35])C=1>O>[N:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]3[CH2:12][NH+:13]([O-:35])[C:14](=[O:26])[C:15]=3[CH:16]=[C:17]3[CH:25]=[CH:24][C:23]4[O:22][CH2:21][O:20][C:19]=4[C:18]=23)=[CH:6][CH:5]=1
Reactant: O=C1NCc2c1cc1ccc3c(c1c2-c1ccncc1)OCO3
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Solvent: O
Product: O=C1c2cc3ccc4c(c3c(-c3ccncc3)c2C[NH+]1[O-])OCO4
Temperature: 25 °C
Reaction time: 2 h
Yield: 39.9 %

Procedure:
To a dichloromethane (100 ml) solution of 8,9-dihydro-10-(4-pyridyl)-7H-1,3-benzodioxolo[4,5-f]isoindol-7-one (200 mg) was added MCPBA (350 mg) and stirred for 2 hours at room temperature. To the reaction mixture was added water. The organic layer was taken and washed with sodium hydrogencarbonate solution and water. The mixture was dried with magnesium sulfate and concentrated to give the entitled compound (84 mg).
Reaction SMILES: [CH2:1]([C@@H:3]1[C@H:6]([C:7]#[C:8][Si](C)(C)C)[NH:5][C:4]1=[O:13])[CH3:2].S(=O)(=O)(O)[OH:15].C(=O)(O)[O-].[Na+]>>[C:7]([C@@H:6]1[NH:5][C:4](=[O:13])[C@@H:3]1[CH2:1][CH3:2])(=[O:15])[CH3:8]
Reactant: O=S(=O)(O)O
Reactant: CC[C@H]1C(=O)N[C@H]1C#C[Si](C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Product: CC[C@H]1C(=O)N[C@H]1C(C)=O

Procedure:
In a similar manner to that of Example 37, (3R,4R)-3-ethyl-4-trimethylsilylethynyl-2-azetidinone (0.18 g) is reacted with mercuric sulfate (0.05 g) and concentrated sulfuric acid (trace). To the reaction mixture is added sodium bicarbonate (0.1 g) and then evaporated under reduced pressure. The residue is extracted with a mixture of ethyl acetate (30 ml) and THF (30 ml), and then evaporated under reduced pressure. The residue is subjected to a column chromatography on silica gel (eluent: 50% ethyl acetate in hexane) to give (3R,4R)-4-acetyl-3-ethyl-2-azetidinone (0.08 g).