Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([Br:24])(Br)(Br)[Br:21].[C:25]([O:29][C:30]([N:32]1[C@@:36]([CH:38]=O)([CH3:37])[CH2:35][O:34][C:33]1([CH3:41])[CH3:40])=[O:31])([CH3:28])([CH3:27])[CH3:26]>ClCCl>[C:25]([O:29][C:30]([N:32]1[C@:36]([CH:38]=[C:20]([Br:24])[Br:21])([CH3:37])[CH2:35][O:34][C:33]1([CH3:41])[CH3:40])=[O:31])([CH3:28])([CH3:26])[CH3:27]
Reactant: BrC(Br)(Br)Br
Reactant: CC(C)(C)OC(=O)N1C(C)(C)OC[C@@]1(C)C=O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1C(C)(C)OC[C@]1(C)C=C(Br)Br
Temperature: 25 °C
Reaction time: 14 h
Yield: 71.8 %

Procedure:
Triphenylphosphine (17.3 g, 65.8 mmol) was dissolved in dichloromethane (25 ml), and a solution of carbon tetrabromide (10.9 g, 32.9 mmol) in dichloromethane (15 ml) was added dropwise thereto in an ice bath followed by stirring for 5 minutes in the ice bath. To the reaction solution was added dropwise a dichloromethane (40 ml) solution of 3-t-butoxycarbonyl-2,2-dimethyl-(4S)-formyl-4-methyloxazolidine (4.00 g, 16.4 mmol) obtained in Reference example 2(c). After stirring for 14 hours at room temperature, insoluble substances of the reaction mixture were filtered out, the filtrate was concentrated under reduced pressure to give the crude title compound (4.70 g, 71.2% yield) as a colorless oil.
Reaction SMILES: C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:32][C:33]([S:47]([CH2:50][C@@H:51]([CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:52](O)=[O:53])(=[O:49])=[O:48])([C:35](=[O:46])[N:36]([CH3:45])[CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)[CH3:34].Cl.Cl.[CH3:64][O:65][C:66](=[O:75])[CH:67]([CH2:69][C:70]1[N:71]=[CH:72][S:73][CH:74]=1)[NH2:68]>C(#N)C>[CH3:64][O:65][C:66](=[O:75])[CH:67]([CH2:69][C:70]1[N:71]=[CH:72][S:73][CH:74]=1)[NH:68][C:52](=[O:53])[C@@H:51]([CH2:50][S:47]([C:33]([CH3:32])([C:35](=[O:46])[N:36]([CH3:45])[CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)[CH3:34])(=[O:49])=[O:48])[CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1
Reactant: CN(CCc1ccccn1)C(=O)C(C)(C)S(=O)(=O)C[C@@H](Cc1ccccc1)C(=O)O
Reactant: COC(=O)C(N)Cc1cscn1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COC(=O)C(Cc1cscn1)NC(=O)[C@H](Cc1ccccc1)CS(=O)(=O)C(C)(C)C(=O)N(C)CCc1ccccn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.5 %

Procedure:
0.28 ml (2.1 mmol) of triethylamine and 265 mg (0.7 mmol) of HBTU were added to a solution of 328 mg (0.7 mmol) of (S)-α-[[[1-methyl-1-[methyl-[2-(2-pyridyl)ethyl]carbamoyl]ethyl]sulfonyl]methyl]hydrocinnamic acid and 181 mg (0.7 mmol) 3-(thiazol-4-yl)-D,L-alanine methyl ester dihydrochloride in 7 ml of acetonitrile and the mixture was stirred at room temperature overnight. Evaporation of the solution under reduced pressure and chromatography of the residue on silica gel using a 200:10:1 mixture of methylene chloride, methanol and ammonia as the eluent yielded 309 mg of N-[(S)-α-[[[1-methyl-1-[methyl-[2-(2-pyridyl)ethyl]carbamoyl]ethyl]sulfonyl]methyl]hydrocinnamoyl]-3-(thiazol-4-yl)-D,L-alanine methyl ester as a colourless foam, MS: 601 (M+H)+.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([CH2:11]O)[CH:2]=1.S(Cl)(Cl)=O.[C-:17]#[N:18].[K+].C([O-])(O)=O.[Na+]>C1C=CC=CC=1>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([CH2:11][C:17]#[N:18])[CH:2]=1
Reactant: [C-]#N
Reactant: OCc1cnc2ccccc2c1
Agent: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O=S(Cl)Cl
Product: N#CCc1cnc2ccccc2c1
Temperature: 25 °C

Procedure:
A solution of quinolin-3-yl-methanol (227, 3.1 g, 19.5 mmol) and thionyl chloride (Aldrich, 16.5 mL, 195 mmol) in 50 mL of benzene was refluxed for 3 h. After cooled to room temperature, the solvent was removed under reduced pressure to dryness. This crude product was used directly in the next reaction. 1H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.82 (s, 1H), 8.21 (d, J=7.9 Hz, 1H), 8.19 (d, J=8.1 Hz, 1H), 7.97 (t, J=7.4 Hz, 1H), 7.81 (t, J=7.5 Hz, 1H), 5.09 (s, 2H). MS (EI): m/z 178 (M+H). Quinolin-3-yl-acetonitrile was synthesized from the above crude product, KCN, NaHCO3 and KI in similar manner as described in Example 221. 1H NMR (400 MHz, DMSO-d6) δ 8.87 (d, J=2.0 Hz, 1H), 8.36 (s, 1H), 8.05 (d, J=8.3 Hz, 1H), 8.03 (d, J=7.8 Hz, 1H), 7.79 (t, J=7.3 Hz, 1H), 7.65 (t, J=7.8 Hz, 1H), 4.31 (s, 2H). MS (EI): m/z 169 (M+H).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].[H-].[Na+].Cl[C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=1.O>CN(C=O)C>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: Clc1ccc2ccccc2n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=[N+]([O-])c1ccc(Oc2ccc3ccccc3n2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
4-Nitrophenol (41 moles, 5.1 g) was dissolved in DMF (500 ml) and treated with sodium hydride (41 mmoles previously washed with hexane). After stirring at room temperature for 1 hr, 2-chloroquinoline (40 moles, 6.5 g) was added dropwise and stirred for 16 hr at room temperature followed by refluxing for 6 hr. Water was added to the cooled solution and the product was extracted with ethyl acetate. The ethyl acetate solution was washed with water, and 5N NaOH, dried over sodium sulfate and concentrated. The product was purified by HPLC over silica gel eluted with ethyl acetate/hexane to yield 2-(4-nitrophenoxy)quinoline. 3.1 mmoles, 8%. Mass Spec (FD) 266. Calcd for C15H10N2O3 : C, 67.45; H, 3.84; N, 10.40. Found: C, 65.84; H, 3.88; N, 8.47.
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH2:10])=[C:4]([NH2:9])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH:11]([N:14]=[C:15]=S)([CH3:13])[CH3:12].CC1C=CC(S([O-])(=O)=O)=CC=1.C[N+]1(CCN=C=NC2CCCCC2)CCOCC1>N1C=CC=CC=1>[Cl:1][C:2]1[C:3]2[N:10]=[C:15]([NH:14][CH:11]([CH3:13])[CH3:12])[NH:9][C:4]=2[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CC(C)N=C=S
Reactant: Nc1cc(Cl)cc(Cl)c1N
Agent: C[N+]1(CCN=C=NC2CCCCC2)CCOCC1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: c1ccncc1
Product: CC(C)Nc1nc2c(Cl)cc(Cl)cc2[nH]1
Yield: 59.9 %

Procedure:
3,5-Dichloro-1,2-phenylenediamine (1.30 g, 7.32 mmol), isopropyl isothiocyanate (0.81 g, 8.00 mmol), 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate (4.19 g, 9.89 mmol) and pyridine (25 mL) were used according to general procedure I. The product was recrystallized from 1,4-dioxane to afford 1.07 g (60%) of a white solid. Anal. calcd for C10H11Cl2N3-(0.25 C4H8O2): C, 49.64; H, 4.92; N, 15.79. Found: C, 49.54; H, 4.94; N, 15.79.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.[F:19][C:20]1[C:21]([NH2:26])=[N:22][CH:23]=[CH:24][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.O1CCOCC1>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:26][C:21]2[C:20]([F:19])=[CH:25][CH:24]=[CH:23][N:22]=2)[CH:7]=1)=[O:18]
Reactant: Nc1ncccc1F
Reactant: O=C(Nc1ccnc(Br)c1)c1c(Cl)cccc1Cl
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: O=C(Nc1ccnc(Nc2ncccc2F)c1)c1c(Cl)cccc1Cl
Yield: 344.6 %

Procedure:
A 25 mL microwave tube containing N-(2-bromopyridin-4-yl)-2,6-dichlorobenzamide (100 mg, 0.29 mmol), 3-fluoropyridin-2-amine (42 mg, 0.38 mmol), Pd2(dba)3 (8 mg, 0.008 mmol), Cs2CO3 (190 mg, 0.58 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 4 mg, 0.003 mmol), and dioxane (15 mL) was degassed and then charged by N2 (3×). The resulting mixture was then irradiated in a microwave reactor at 130° C. for 30 min. The mixture was diluted with dioxane (20 mL) and filtered through Celite. The filtrate was concentrated under reduced pressure and the residue was purified by reverse-phase HPLC (Gemini, 200 mm×25 mm, gradient: CH3CN/0.05% NH3.H2O, 50-80%, 10 min) to afford the desired product (377 mg, yield: 45%). 1H NMR (400 MHz, DMSO) δ 11.07 (s, 1H), 8.98 (s, 1H), 8.28-8.01 (m, 3H), 7.70-7.48 (m, 4H), 7.37 (s, 1H), 7.01 (s, 1H). LCMS (ESI) m/z: 378.5 [M+H+].
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([CH2:16][C:15](=[O:17])[C:14]3[C:9](=[CH:10][CH:11]=[C:12](Br)[CH:13]=3)[O:8]2)[CH2:4][CH2:3]1.COC(=O)/C=C/C1C=C2C(=CC=1)OC1(CCN(C(OC(C)(C)C)=O)CC1)CC2=O.[C:48]([O:52][C:53](=[O:56])[CH:54]=[CH2:55])([CH3:51])([CH3:50])[CH3:49]>>[C:48]([O:52][C:53](=[O:56])/[CH:54]=[CH:55]/[C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[O:8][C:5]1([CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1)[CH2:16][C:15]2=[O:17])([CH3:51])([CH3:50])[CH3:49]
Reactant: C=CC(=O)OC(C)(C)C
Reactant: CN1CCC2(CC1)CC(=O)c1cc(Br)ccc1O2
Agent: COC(=O)/C=C/c1ccc2c(c1)C(=O)CC1(CCN(C(=O)OC(C)(C)C)CC1)O2
Product: CN1CCC2(CC1)CC(=O)c1cc(/C=C/C(=O)OC(C)(C)C)ccc1O2

Procedure:
(E)-3-{1′-Methyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid tert-butyl ester was synthesized starting from 1′-methyl-6-bromo-spiro[chromane-2,4′-piperidine]-4-one (1.62 g, 5.22 mmol) according to the procedure for preparation of Intermediate 1, Step B, using tert-butylacrylate, giving a yellow solid (1.45 g). The resulting product was dissolved in a 20% TFA/DCM mixture (25 ml) and stirred at RT. After 16 h, the solvent was evaporated and the residue was partitioned between DCM and a saturated NaHCO3 solution. Then the aqueous phase was acidified with a 6 M solution of HCl and evaporated. The residue was suspended in a 9:1 DCM/MeOH mixture (70 ml) and the insoluble salts were filtered off. The solvent was dried over Na2SO4 and evaporated, giving (E)-3-{1′-methyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (890 mg) as a yellow solid.
Reaction SMILES: [OH-].[K+].[CH3:3][O:4][C:5](=[O:31])[CH:6]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.[Br:32][CH2:33][CH2:34]Br>C(O)C>[CH3:3][O:4][C:5](=[O:31])[CH:6]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH2:34][CH2:33][Br:32])=[CH:12][CH:13]=1
Reactant: BrCCBr
Reactant: COC(=O)C(Cc1ccc(O)cc1)Nc1ccccc1C(=O)c1ccc(F)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: COC(=O)C(Cc1ccc(OCCBr)cc1)Nc1ccccc1C(=O)c1ccc(F)cc1
Yield: 37.9 %

Procedure:
To a solution of potassium hydroxide (0.17 g, 2.95 mmol) in ethanol (20 ml) is added 2-[(2-(4-fluorobenzoyl)phenyl)amino]-3-(4-hydroxyphenyl)-propionic acid methyl ester (1.16 g, 2.95 mmol) and 1,2-dibromoethane (5.54 g, 29.50 mmol). Then the mixture is heated to reflux for 8 hours. After cooled, the reaction mixture is filtered to remove the solid formed, and then the filtrate is evaporated under a vacuum. The crude product is purified by silica gel chromatography using hexane/EtOAc (4:1) as eluent to give the title compound (0.56 g, 38%).
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].Br[C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:20][C@@H:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:18][C:17]2=[O:27])=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:20][C@@H:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:18][C:17]2=[O:27])=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: C=CCCCCCC
Reactant: O=C1O[C@H](c2ccccc2)CN1c1ccc(Br)cc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCCCCCCCc1ccc(N2C[C@@H](c3ccccc3)OC2=O)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 17 %

Procedure:
0.40 g (3.56 mM) of 1-octene and 2 ml of dry tetrahydrofuran (THF) were placed in 50 ml-three necked flask. To the mixture, 7.6 ml of 0.5M-9-borabicyclo[3.3.1]-nonane-(9-BBN) in THF was gradually added dropwise on an ice-common salt bath at -15° to -13° C. (inner temperature) in nitrogen atmosphere, followed by stirring for 1 hour at the same temperature and further stirring for 2 hours at about 10° C. To the resultant mixture, a solution of 0.80 g (2.51 mM) of (5R)-3-(4-bromophenyl)-5-phenyl-2-oxazolidinone synthesized in Example 3 in 11 ml of DMF was added under cooling on an ice bath, followed by addition of 0.08 g of tetrakis (triphenylphosphine) palladium (O) and 0.70 g of potassium carbonate in succession and then stirring for 3 hours at 63.5°-70 ° C. (inner temperature). After the reaction, the reaction mixture was poured into ice water to precipitate a crystal. The crystal was recovered by filtration and washed with water, followed by purification by silica gel column chromatography (eluent: hexane/ethyl acetate=4/1) and recrystallization from acetone to obtain 0.15 g of (5R)-3-(4-octylphenyl)-5-phenyl-2-oxazolidinone (Yield: 17.0%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:25])[C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[N:19]1[CH:23]=[N:22][N:21]=[C:20]1[CH3:24].[CH2:26]=[O:27]>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:25])[C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:16])[F:17])[CH:12]=[CH:11][C:10]=1[N:19]1[C:20]([CH3:24])=[N:21][N:22]=[C:23]1[CH2:26][OH:27]
Reactant: C=O
Reactant: Cc1nncn1-c1ccc(C(F)(F)F)cc1C(=O)c1ccccc1Cl
Solvent: Cc1ccccc1C
Product: Cc1nnc(CO)n1-c1ccc(C(F)(F)F)cc1C(=O)c1ccccc1Cl
Temperature: 122 °C

Procedure:
In the manner given in Example 4, 2'-chloro-5-(trifluoromethyl)-2-(3-methyl-4H-1,2,4-triazol-4-yl)benzophenone, paraformaldehyde and xylene are warmed under nitrogen to about 122° C. to give 2'-chloro-5-(trifluoromethyl)-2-[3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4-yl]benzophenone.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]([C:22]3[O:23][C:24]4[C:29]([C:30](=[O:39])[C:31]=3[C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=3)=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH3:21])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([O:17]C)[CH:14]=[C:13]([F:19])[CH:12]=3)[C:3]=12>ClCCl.B(Br)(Br)Br>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]([C:22]3[O:23][C:24]4[C:29]([C:30](=[O:39])[C:31]=3[C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=3)=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH3:21])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([OH:17])[CH:14]=[C:13]([F:19])[CH:12]=3)[C:3]=12
Reactant: COc1cc(F)cc(-c2nn(C(C)c3oc4ccccc4c(=O)c3-c3cccc(F)c3)c3ncnc(N)c23)c1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CC(c1oc2ccccc2c(=O)c1-c1cccc(F)c1)n1nc(-c2cc(O)cc(F)c2)c2c(N)ncnc21
Temperature: 25 °C
Reaction time: 12 h
Yield: 51.5 %

Procedure:
To a solution of Example 76 (0.160 g, 0.304 mmoles) in dichloromethane (25 ml), BBr3 (1M in dichloromethane, 1.6 ml) was added at 0° C. and the reaction mixture was warmed to RT and then stirred for 12 h. The reaction mixture was quenched with 1.5N HCl solution and extracted with dichloromethane. The organic layer was dried over sodium sulphate and concentrated. The crude product was purified by column chromatography with methanol: dichloromethane to afford the title compound as off-white solid (0.080 g, 51% yield). MP: 271-273° C. 1H-NMR (δ ppm, DMSO-D6, 400 MHz): δ 10.17(s,1H), 8.06(s, 1H), 8.05(dd, J=7.9,1.4Hz, 1H), 7.86(dt, J=8.5,1.5Hz, 1H), 7.68(d, J=8.3Hz, 1H),7.53(t, J=7.9Hz, 1H), 7.28(br s, 1H), 7.05(dt, J=6.8,2.0 Hz, 1H), 6.91(br s, 2H), 6.86(s,1H), 6.79(d, J=9.4Hz, 1H), 6.66(td, J=10.3,2.1 Hz, 1H),6.05(q, J=6.7Hz, 1H),1.88(d, J=7.1Hz, 3H). Mass: 511.80(M+).
Reaction SMILES: [CH3:1][N:2]([CH2:4][CH2:5]Cl)[CH3:3].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]3[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:18]=3[C:19]=2[C:20](=[O:28])[C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=2)=[CH:11][CH:10]=1>>[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]3[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:18]=3[C:19]=2[C:20](=[O:28])[C:21]2[CH:26]=[CH:25][C:24]([O:27][CH2:5][CH2:4][N:2]([CH3:3])[CH3:1])=[CH:23][CH:22]=2)=[CH:11][CH:10]=1
Reactant: CN(C)CCCl
Reactant: COc1ccc(-c2oc3cc(OC)ccc3c2C(=O)c2ccc(O)cc2)cc1
Product: COc1ccc(-c2oc3cc(OC)ccc3c2C(=O)c2ccc(OCCN(C)C)cc2)cc1

Procedure:
The title compound was prepared essentially as described in Example 24, supra, except that 2-(N,N-dimethylamino)ethyl chloride was reacted with 2-(4-methoxyphenyl)-3-(4-hydroxybenzoyl)-6-methoxybenzofuran instead of the 2-(N,N-diisopropylamino)ethyl chloride employed in that example.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][OH:14])[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:15]I>>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][O:14][CH3:15])[CH:10]([CH3:11])[CH3:12])=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)[C@H](CO)NC(=O)OC(C)(C)C
Reactant: CI
Product: COC[C@H](NC(=O)OC(C)(C)C)C(C)C
Yield: 67 %

Procedure:
The title compound has been prepared in 67% yield from the alcohol of Example 6, Step B and methyl iodide following the alkylation method given in Example 6, Step C.
Reaction SMILES: C[O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:14].CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([CH3:45])(=[O:44])=[O:43])=[CH:38][C:37]=1[C:46]([F:49])([F:48])[F:47]>CN(C=O)C>[CH3:45][S:42]([C:39]1[CH:40]=[CH:41][C:36]([CH2:35][N:7]2[C:8]3=[N:9][CH:10]=[CH:11][CH:12]=[C:13]3[C:5]([CH2:4][C:3]([OH:2])=[O:15])=[C:6]2[CH3:14])=[C:37]([C:46]([F:47])([F:49])[F:48])[CH:38]=1)(=[O:44])=[O:43]
Reactant: COC(=O)Cc1c(C)[nH]c2ncccc12
Reactant: CS(=O)(=O)c1ccc(CBr)c(C(F)(F)F)c1
Agent: CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C
Solvent: CN(C)C=O
Product: Cc1c(CC(=O)O)c2cccnc2n1Cc1ccc(S(C)(=O)=O)cc1C(F)(F)F
Temperature: 10 °C
Reaction time: 0.67 h

Procedure:
To an ice-cooled solution of (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester ((12.8 g, 62.8 mmol) in dry DMF (400 ml) under an inert atmosphere of Argon is added dropwise, BEMP (18.1 ml, 62.8 mmol) over two minutes. After stirring at 10° C. for 40 minutes, the resulting solution is treated dropwise with 1-bromomethyl-4-methanesulfonyl-2-trifluoromethyl-benzene (23.8 g, 75.4 mmol) and allowed to warm to room temperature while stirring overnight. The reaction is concentrated in vacuo with toluene azeotroping and the resulting oil is partitioned between water (400 ml) and DCM (500 ml) and extracted with DCM (500 ml). The organic portions are combined and washed with water (2×200 ml). The resulting suspension is filtered and concentrated in vacuo with toluene azeotroping. The crude is purified by chromatography on silica eluting with iso-hexane/acetone (16:4) to yield the titled product. (MH+ 441)
Reaction SMILES: [F:1][CH:2]([F:35])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[CH:20][C:21]([CH2:24][NH:25]C(=O)OC(C)(C)C)=[N:22][CH:23]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:34])[CH3:33])=[O:4].N1C(C)=CC=CC=1C.[Si](OS(C(F)(F)F)(=O)=O)(C(C)(C)C)(C)C.[NH4+].[Cl-].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(Cl)Cl>[NH2:25][CH2:24][C:21]1[N:22]=[CH:23][C:18]([C:15]2[CH:14]=[CH:13][C:12]([C@H:8]3[O:7][C:6]([CH3:33])([CH3:34])[N:5]([C:3](=[O:4])[CH:2]([F:35])[F:1])[C@@H:9]3[CH2:10][F:11])=[CH:17][CH:16]=2)=[CH:19][CH:20]=1
Reactant: CC(C)(C)OC(=O)NCc1ccc(-c2ccc([C@H]3OC(C)(C)N(C(=O)C(F)F)[C@@H]3CF)cc2)cn1
Agent: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Product: CC1(C)O[C@H](c2ccc(-c3ccc(CN)nc3)cc2)[C@@H](CF)N1C(=O)C(F)F
Temperature: 25 °C
Reaction time: 18 h
Yield: 6.9 %

Procedure:
To a solution of tert-butyl (5-(4-((4S,5R)-3-(2,2-difluoroacetyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)pyridin-2-yl)methylcarbamate (970 mg, 4.5 mmol) in CH2Cl2 (25 mL) at 0° C. is added 2,6-lutidine (4604, 3.9 mmol) followed by t-butyldimethylsilyltrifluoromethanesulfonate (7004, 2.9 mmol). The reaction is stirred at room temperature for 18 hours. Additional lutidine (2304, 1.9 mmol) and t-butyldimethylsilyltrifluoromethanesulfonate (3504, 1.4 mmol) is added and contents heated to 35° C. for 1 hour. Saturated NH4Cl is added and the reaction is stirred for 15 minutes. Contents are diluted with CH2Cl2 and separated. The organic phase is washed with saturated NH4Cl, saturated NaHCO3, brine, dried (Na2SO4) and concentrated under vacuum. Crude silyl carbamate is dissolved in tetrahydrofuran (20 mL) and tetrabutylammonium fluoride (0.6 mL, 2.0 mmol) is added and stirred for 20 minutes. Saturated NH4Cl is added and contents are extracted with ethylacetate. The organic phase is washed successively with saturated sodium hydrogen carbonate, brine, dried with Na2SO4 and concentrated under vacuum to afford the title compound (123 mg): m/z (Cl) M+H 394.
Reaction SMILES: C[O:2][C:3](=[O:22])[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([S:12](=[O:21])(=[O:20])[NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:7]=1.[OH-].[Na+]>CO>[C:14]1([NH:13][S:12]([C:8]2[CH:7]=[C:6]([CH:5]=[CH:4][C:3]([OH:22])=[O:2])[CH:11]=[CH:10][CH:9]=2)(=[O:21])=[O:20])[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: COC(=O)C=Cc1cccc(S(=O)(=O)Nc2ccccc2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)C=Cc1cccc(S(=O)(=O)Nc2ccccc2)c1
Reaction time: 0.5 h
Yield: 82.7 %

Procedure:
3-(3-Phenylsulfamoylphenyl)acrylic acid methyl ester (4a) (0.220 g, 0.69 mmol) was dissolved in methanol (3 ml), 1 N NaOH (2.08 ml, 2.08 mmol) was added and the resultant solution was stirred at ambient temperature overnight. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was acidified with 10% HCl and stirred for 30 min. The precipitated solid was filtered, washed with water and dried in desiccator over P2O5 to give the title compound as a white solid (0.173 g, 82%).
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]2[N:11]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[C:10](=[O:20])[N:9]([CH2:21][C:22]#[N:23])[N:8]=2)=[CH:4][CH:3]=1.Cl.[NH2:25][OH:26].C(N(CC)CC)C>C(O)C>[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:11]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[C:10](=[O:20])[N:9]([CH2:21]/[C:22](=[N:25]/[OH:26])/[NH2:23])[N:8]=2)=[CH:4][CH:3]=1
Reactant: NO
Reactant: N#CCn1nc(-c2ccc(Cl)s2)n(Cc2ccccc2F)c1=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: N/C(Cn1nc(-c2ccc(Cl)s2)n(Cc2ccccc2F)c1=O)=N\O
Reaction time: 1 h

Procedure:
250 mg (0.66 mmol) of the compound from Example 24A and 92 mg (1.32 mmol) of hydroxylamine hydrochloride were suspended in 3.3 ml of ethanol, and the mixture was heated to the boil. 193 μl (1.39 mmol) of triethylamine were added to the hot solution and heating under reflux was continued for a further 1 h. On cooling of the reaction, a colorless solid crystallized out; this solid was filtered off and washed with a little ethanol. This gave 174 mg (69% of theory) of the target compound as a colorless solid. The mother liquor was concentrated under reduced pressure on a rotary evaporator, and the residue was partitioned between water and ethyl acetate. The organic phase was washed successively with 10 ml of water and 10 ml of saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. This gave a further 69 mg (24% of theory) of the target compound in a purity of 87% as a slightly yellowish solid.