Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C(O)=O.[C:8]1([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH:17]=[CH:16][C:15]=2[NH:26][C:27]([C:29]2[NH:30][CH:31]=[C:32]([C:34]#[N:35])[N:33]=2)=[O:28])[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]=1.CCN(CC)CC.C[Si]([N:47]=[C:48]=[O:49])(C)C>C(Cl)Cl>[C:34]([C:32]1[N:33]=[C:29]([C:27]([NH:26][C:15]2[CH:16]=[CH:17][C:18]([CH:20]3[CH2:21][CH2:22][N:23]([C:48]([NH2:47])=[O:49])[CH2:24][CH2:25]3)=[CH:19][C:14]=2[C:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]=2)=[O:28])[NH:30][CH:31]=1)#[N:35]
Reactant: C[Si](C)(C)N=C=O
Reactant: N#Cc1c[nH]c(C(=O)Nc2ccc(C3CCNCC3)cc2C2=CCCCC2)n1
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N#Cc1c[nH]c(C(=O)Nc2ccc(C3CCN(C(N)=O)CC3)cc2C2=CCCCC2)n1
Temperature: 25 °C
Reaction time: 10 h
Yield: 71.7 %

Procedure:
A flask was charged with 4-cyano-1H-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide TFA salt (51 mg, 0.10 mmol) (as prepared in Example 14, step (b)), NEt3 (22 μL, 0.15 mmol), trimethylsilyl isocyanate (16 μL, 0.11 mmol) and 1.0 mL of DCM and stirred for 10 h at 25° C. The solvent was evaporated and the title compound was purified by RP-HPLC (C18), eluting with 35-60% CH3CN in 0.1% TFA/H2O over 11 min to give 30 mg (70%) of a white solid. 1H-NMR (400 MHz, DMSO-d6): δ 14.28 (br s, 1H), 9.76 (s, 1H), 8.34 (s, 1H), 7.84 (d, 1H), 7.18 (dd, 1H), 7.08 (d, 1H), 6.00 (br s, 2H), 5.72 (m, 1H), 4.18 (m, 2H), 2.80-2.60 (m, 3H), 2.24-2.10 (m, 4H), 1.80-1.60 (m, 6H), 1.50 (m, 2H). Mass spectrum (ESI, mnz): Calcd. for C23H26N6O, 419.2 (M+H), found 419.0.
Reaction SMILES: [F:1][CH:2]([F:14])[N:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[O:12][C:11](S)=[N:10][N:9]=1.F[CH:16](F)[N:17]1[CH:21]=[CH:20][CH:19]=[C:18]1[C:22]([NH:24]N)=O.F[C:28](F)(F)N1C=CC=C1C(OC)=O.N1C=CC=C1C(OC)=O>>[N:17]12[CH2:21][CH2:20][CH:19]([CH2:28][CH2:16]1)[N:24]([C:11]1[O:12][C:8]([C:4]3[N:3]([CH:2]([F:14])[F:1])[CH:7]=[CH:6][CH:5]=3)=[N:9][N:10]=1)[CH2:22][CH2:18]2
Reactant: NNC(=O)c1cccn1C(F)F
Reactant: COC(=O)c1cccn1C(F)(F)F
Reactant: FC(F)n1cccc1-c1nnc(S)o1
Agent: COC(=O)c1ccc[nH]1
Product: FC(F)n1cccc1-c1nnc(N2CCN3CCC2CC3)o1

Procedure:
May be prepared according to Methods A-D from 5-[1-(difluoromethyl)pyrrol-2-yl]-1,3,4-oxadiazole-2-thiol (Method A), from 1-(difluoromethyl)pyrrole-2-carbohydrazide (Method B), from methyl 1-(trifluoromethyl)pyrrole-2-carboxylate (Method C), and from methyl 1H-pyrrole-2-carboxylate (Method D).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]([C:11]([NH2:13])=[O:12])[NH2:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.O.[C:15]1([C:21]([CH:23]=O)=O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:11](=[O:12])[N:13]=[C:21]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:23]=[N:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: NC(=O)N(N)c1cc(Cl)cc(Cl)c1
Reactant: O=CC(=O)c1ccccc1
Solvent: C1COCCO1
Solvent: O
Product: O=c1nc(-c2ccccc2)cnn1-c1cc(Cl)cc(Cl)c1
Yield: 42.2 %

Procedure:
In 50 ml of dioxane was dissolved 2.20 g of 2-(3,5-dichlorophenyl)semicarbazide followed by addition of 1.52 g of phenylglyoxal monohydrate, and the mixture was refluxed for 5 hours. The reaction mixture was then concentrated and the residue was recrystallized from acetonitrile to provide 1.34 g of the title compound. m.p. 160-161° C.
Reaction SMILES: [Br:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.C(N(C(C)C)C(C)C)C.[CH2:18]([Si:20]([CH2:28][CH3:29])([CH2:26][CH3:27])[CH2:21][CH2:22][O:23][CH2:24]Cl)[CH3:19].O>C(Cl)(Cl)Cl>[Br:1][C:2]1[C:7]([O:8][CH2:24][O:23][CH2:22][CH2:21][Si:20]([CH2:26][CH3:27])([CH2:18][CH3:19])[CH2:28][CH3:29])=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: Oc1cccnc1Br
Reactant: CC[Si](CC)(CC)CCOCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClC(Cl)Cl
Solvent: O
Product: CC[Si](CC)(CC)CCOCOc1cccnc1Br
Temperature: 25 °C
Reaction time: 2 h
Yield: 68 %

Procedure:
To a solution of 2-bromo-3-hydroxypyridine (15 g, 0.0862 mol) in chloroform (260 mL), ethyldiisopropylamine (18 mL, 0.103 mol) and 2-(triethylsilyl)ethoxymethyl chloride (16.7 mL, 0.0948 mol) were added at 0° C. After the mixture was stirred at room temperature for 2 hours, water (50 mL) was added thereto and the precipitated insoluble materials were filtered off. The organic layer of the filtrate was separated, washed with water, and then dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to give 2-bromo-3-[2-(triethylsilyl)ethoxymethoxy]pyridine (20.3 g, 77%) as a light-yellow oil.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][OH:13].[OH:14][C:15]1[CH:20]=[C:19]([OH:21])[CH:18]=[CH:17][C:16]=1[C:22]1[N:27]=[C:26]([C:28]2[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][C:29]=2[OH:35])[N:25]=[C:24]([C:36]2[CH:41]=[CH:40][C:39]([OH:42])=[CH:38][C:37]=2[OH:43])[N:23]=1.[OH-:44].[K+]>>[OH:14][C:15]1[CH:20]=[C:19]([O:21][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][OH:13])[CH:18]=[CH:17][C:16]=1[C:22]1[N:23]=[C:24]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][OH:44])=[CH:38][C:37]=2[OH:43])[N:25]=[C:26]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][OH:13])=[CH:30][C:29]=2[OH:35])[N:27]=1
Reactant: OCCCCCCCCCCCBr
Reactant: Oc1ccc(-c2nc(-c3ccc(O)cc3O)nc(-c3ccc(O)cc3O)n2)c(O)c1
Reactant: [OH-]
Agent: [K+]
Product: OCCCCCCCCCCCOc1ccc(-c2nc(-c3ccc(OCCCCCCCCCCCO)cc3O)nc(-c3ccc(OCCCCCCCCCCCO)cc3O)n2)c(O)c1
Temperature: 100 °C
Yield: 53 %

Procedure:
Under nitrogen, 42.9 g (170 mmol) of 11-bromo-1-undecanol are added at 80° C. to 2,4,6-tris(2,4-dihydroxyphenyl)-1,3,5-triazine, 9.3 g (141 mmol) of potassium hydroxide and 150 ml of diglyne. The mixture is heated at 100° C. for 16 hours and filtered while hot, and the filtrate is cooled to 0° C. The crystallized solid is filtered off, pressed and dried for 48 hours under reduced pressure (60 mmHg, 70° C.), giving 24.3 g (53% yield) of 2,4,6-tris[2-hydroxy-4-(11-hydroxyundecyloxy)phenyl]-1,3,5-triazine as a pale yellow, resin-like solid.
Reaction SMILES: [Cl:1][C:2]1[C:3]([OH:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10]([C:12]#[N:13])=[CH:9][CH:8]=[CH:7]2.[Br:15]Br.O>C(O)(=O)C>[Br:15][C:8]1[CH:9]=[C:10]([C:12]#[N:13])[C:11]2[C:6]([CH:7]=1)=[CH:5][CH:4]=[C:3]([OH:14])[C:2]=2[Cl:1]
Reactant: N#Cc1cccc2ccc(O)c(Cl)c12
Reactant: BrBr
Solvent: O
Solvent: CC(=O)O
Product: N#Cc1cc(Br)cc2ccc(O)c(Cl)c12
Temperature: 100 °C
Reaction time: 8 h
Yield: 56.2 %

Procedure:
To a mixture of 8-chloro-7-hydroxy-1-naphthonitrile (0.127 g, 0.63 mmol) and glacial acetic acid (1 mL) in a pressure tube was added a solution of bromine (0.24 g, 1.5 mmol) in glacial acetic acid (2 mL). The tube was sealed and the mixture was stirred at 100° C. overnight. The reaction was cooled, poured into water (50 mL), and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with sodium bicarbonate solution, dried over sodium sulfate, filtered, stripped of solvent, and purified on a silica column (20% ethyl acetate—hexanes) to yield 0.10 g (56%) of the title compound as a yellow solid. An analytical sample was prepared by preparative reverse phase HPLC to yield the title compound as a white solid: mp 148-150° C.; 1H NMR (DMSO-d6): δ 7.47 (1H, d, J=8.98 Hz), 7.95 (1H, d, J=9.02 Hz), 8.32 (1H, d, J=2.08 Hz), 8.55 (1H, d, J=2.08 Hz), 11.33 (1H, s); MS (ESI) m/z 280/282/284 (M−H)−.
Reaction SMILES: CO[C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][CH2:9][CH2:10][NH:11][C:12]([C:14]2[S:15][CH:16]=[CH:17][C:18]=2[NH:19][C:20]2[CH:25]=[CH:24][N:23]=[C:22]3[NH:26][CH:27]=[CH:28][C:21]=23)=[O:13])=[CH:5][CH:4]=1.[CH3:31]C1C=CC(C=O)=CC=1>>[CH3:31][C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][CH2:9][CH2:10][NH:11][C:12]([C:14]2[S:15][CH:16]=[CH:17][C:18]=2[NH:19][C:20]2[CH:25]=[CH:24][N:23]=[C:22]3[NH:26][CH:27]=[CH:28][C:21]=23)=[O:13])=[CH:5][CH:4]=1
Reactant: COc1ccc(CNCCNC(=O)c2sccc2Nc2ccnc3[nH]ccc23)cc1
Reactant: Cc1ccc(C=O)cc1
Product: Cc1ccc(CNCCNC(=O)c2sccc2Nc2ccnc3[nH]ccc23)cc1

Procedure:
This compound was prepared in an analogous manner as 3-(1H-Pyrrolo[2,3-b]pyridin-4-ylamino)-thiophene-2-carboxylic acid [2-(4-methoxy-benzylamino)-ethyl]amide using 4-methylbenzaldehyde instead of 4-methoxy benzaldehyde. LCMS (ESI) 406 (M+H) 1H NMR (400 MHz, DMSO-d6) δ ppm 11.43-11.53 (1H, m) 10.24 (1H, s) 7.95-8.04 (1H, m) 7.75 (1H, d, J=5.47 Hz) 7.44 (1H, d, J=5.47 Hz) 7.25-7.31 (1H, m) 7.14 (1H, d, J=8.00 Hz) 7.03 (1H, d, J=7.81 Hz) 6.77 (1H, d, J=5.47 Hz) 6.41 (1H, dd, J=3.42, 1.85 Hz) 3.60 (2H, s) 3.31-3.36 (2H, m) 2.58 (2H, t, J=6.54 Hz) 2.22 (3H, s)
Reaction SMILES: [Cl:1][C:2]1[C:11]([CH2:12]O)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.P(Br)(Br)[Br:15]>C(Cl)(Cl)Cl>[Br:15][CH2:12][C:11]1[C:2]([Cl:1])=[N:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2
Reactant: OCc1cc2ccccc2nc1Cl
Reactant: BrP(Br)Br
Solvent: ClC(Cl)Cl
Product: Clc1nc2ccccc2cc1CBr
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
To a solution of (2-chloroquinolin-3-yl)methanol (0.96 g, 4.95 mmol) in anhydrous chloroform at 0° C. was added phosphorous tribromide (1.34 g, 4.95 mmol). After stirring at room temperature for 2 hours, the solvent was evaporated to provide 3-(bromomethyl)-2-chloroquinoline (1.27 g), which was used in the next step without purification.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=O)=[C:4]([Cl:11])[CH:3]=1.Cl[C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][N:14]=1.ClC1C=C(Cl)C=CC=1C1[C:36]([C:37]2[NH:38][CH:39]=[CH:40][N:41]=2)=[CH:35][N:34]=[C:33]([NH:42][CH2:43][CH2:44][NH:45]C2C=CC([N+]([O-])=O)=CN=2)[N:32]=1>>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]2[C:36]([C:37]3[NH:38][CH:39]=[CH:40][N:41]=3)=[CH:35][N:34]=[C:33]([NH:42][CH2:43][CH2:44][NH:45][C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][N:14]=3)[N:32]=2)=[C:4]([Cl:11])[CH:3]=1
Reactant: FC(F)(F)c1ccc(Cl)nc1
Reactant: O=[N+]([O-])c1ccc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)nc1
Reactant: O=C(Cl)c1ccc(Br)cc1Cl
Product: FC(F)(F)c1ccc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Br)cc3Cl)n2)nc1

Procedure:
[4-(4-bromo-2-chlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl](2-{[5-(trifluoromethyl)(2-pyridyl)]amino}ethyl)amine was prepared from 4-bromo-2-chlorobenzoyl chloride and 2-chloro-5-(trifluoromethyl)pyridine using the general method for [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]{2-[(5-nitro(2-pyridyl))amino]ethyl}amine.
Reaction SMILES: C[Si](C)(C)[CH:3]1[S:8][CH2:7][CH2:6][CH2:5][S:4]1.C([Li])CCC.[F:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[O:23][CH2:22][CH2:21][C:20]2=O.O>CCCCCC.O1CCCC1>[S:4]1[CH2:5][CH2:6][CH2:7][S:8][C:3]1=[C:20]1[C:19]2[CH:18]=[C:17]([F:16])[CH:26]=[CH:25][C:24]=2[O:23][CH2:22][CH2:21]1
Reactant: C[Si](C)(C)C1SCCCS1
Reactant: O=C1CCOc2ccc(F)cc21
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCC
Product: Fc1ccc2c(c1)C(=C1SCCCS1)CCO2
Temperature: 0 °C
Reaction time: 8 h

Procedure:
28.8 g of 2-trimethylsilyl-1,3-dithiane were dissolved in 290 ml of peroxide-free tetrahydrofuran and the solution was treated dropwise at -60° C. with 93 ml of a 1.6M solution of n-butyl lithium in hexane. The mixture was left to warm to 0° C. within 3 hours and subsequently again cooled to -60° C. A solution of 24.87 g of 6-fluoro-4-chromanone in 150 ml of tetrahydrofuran was subsequently slowly added dropwise and the mixture was left to warm slowly from -60° C. to room temperature while stirring overnight. The mixture was subsequently poured into 2.5 l of water and extracted with four portions of ethyl acetate. The organic extracts were washed with saturated sodium chloride solution and dried with sodium sulfate The concentrated extract was decolorized with active carbon in a mixture of ether and low-boiling petroleum ether (1:1) and crystallized from the same mixture in the cold. After two recrystallizations, the combined mother liquors were chromatographed on a silica gel 60 column [hexane/ethyl acetate (9:1)]. The product-containing fractions were concentrated and the residue was recrystallized. There was obtained 4-m-dithian-2-ylidene-6-fluoro-2,3-dihydro-4H-1-benzopyran of melting point 47°-49° C.
Reaction SMILES: [N:1]([C:4]1([CH3:19])[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][CH2:6][CH:5]1[OH:18])=[N+]=[N-].CP(C)C>C1COCC1.O>[NH2:1][C:4]1([CH3:19])[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:7][CH2:6][CH:5]1[OH:18]
Reactant: CC1(N=[N+]=[N-])CCN(Cc2ccccc2)CCC1O
Agent: CP(C)C
Solvent: O
Solvent: C1CCOC1
Product: CC1(N)CCN(Cc2ccccc2)CCC1O
Temperature: 65 °C
Reaction time: 18 h
Yield: 88.9 %

Procedure:
To a solution of 5-azido-1-benzyl-5-methylazepan-4-ol (1.5 g, 5.76 mmol) in THF (12 mL) and water (4 mL) was added slowly a solution of trimethylphosphine (1 M in toluene, 28 mL, 28.9 mmol) and the reaction was stirred at 65° C. for 18 hr. The mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was dissolved in 1 M HCl (30 mL) and extracted with EtOAc (2×25 mL). The aqueous layer was basified to pH14 with aqueous 6 M NaOH and extracted with DCM (3×30 mL). The combined organic layers were passed through a phase separation cartridge concentrated under reduced pressure. Purification via silica gel column chromatography (1-10% 7 M NH3 in MeOH/DCM) gave 5-amino-1-benzyl-5-methylazepan-4-ol as a viscous yellow oil (1.2 g, 89%). 1H NMR (400 MHz, CDCl3) δ 7.34-7.20 (m, 5H), 3.60-3.52 (m, 2H), 3.50-3.46 (m, 2H), 2.80-2.79 (m, 1H), 2.70-2.45 (m, 4H), 2.15-1.95 (m, 1H), 1.79-1.72 (m, 2H), 1.49-1.40 (m, 2H), 1.19 (s, 3H).
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][C:10]([NH:12][CH2:13][C:14]([OH:16])=O)=[O:11])=[O:7])([CH3:4])[CH3:3].[NH2:17][C@H:18]([C:26]([O:28]C)=O)[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O.[NH2:31][NH2:32]>CO>[NH:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:9][C:10]([NH:12][CH2:13][C:14]([NH:17][C@H:18]([C:26]([NH:31][NH2:32])=[O:28])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:16])=[O:11]
Reactant: NN
Reactant: COC(=O)[C@@H](N)Cc1ccccc1
Reactant: CC(C)(C)OC(=O)NCC(=O)NCC(=O)O
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)NCC(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)NN
Reaction time: 24 h

Procedure:
Boc-Gly-GLy-Phe-OMe (8.0 g., 20 mM) was dissolved in methanol (25 ml.), and 95% v/v hydrazine hydrate (3.2 ml.) was added. The mixture was kept at room temperature for 24 hours and then evaporated. The residue was chromatographed on a column of silica gel equibrated and eluted with methanol/chloroform 1:9 v/v. The fractions which contained the required hydrazide were combined and evaporated to give Boc-Gly-Gly-Phe-NHNH2, RfP 0.6, RfQ 0.3.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][OH:10].[C:11]([O-])([O-])=O.[Cs+].[Cs+].CI>CC(C)=O>[OH:10][CH2:9][CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[O:1][CH3:11]
Reactant: OCCc1ccccc1O
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CI
Solvent: CC(C)=O
Product: COc1ccccc1CCO
Temperature: 25 °C
Reaction time: 0.83 h

Procedure:
To a solution of 10 g of 2-(2-hydroxyphenyl)-ethanol in 200 ml of acetone there are added 35.3 g of Cs2CO3 and then a solution of 6.5 ml of methyl iodide in 40 ml of acetone. The reaction mixture is stirred for 50 minutes at room temperature, is filtered and is concentrated by evaporation. The residue is partitioned between diethyl ether and water. The organic phases are combined, dried over magnesium sulfate and concentrated by evaporation, and the residue is purified by means of FC (dichloromethane/diethyl ether=97:3), yielding the title compound: Rf (dichloromethane/diethyl ether=97:3)=0.34; HPLC Rt =9.31 minutes.
Reaction SMILES: [CH2:1]1[CH:5]([OH:6])[CH2:4][NH:3][CH2:2]1.C(N(CC)CC)C.[CH2:14]([O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1)[CH2:15][CH2:16][CH3:17].C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.O>[CH2:14]([O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([N:3]2[CH2:2][CH2:1][CH:5]([OH:6])[CH2:4]2)(=[O:27])=[O:26])=[CH:21][CH:20]=1)[CH2:15][CH2:16][CH3:17]
Reactant: OC1CCNC1
Reactant: CCCCOc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CCCCOc1ccc(S(=O)(=O)N2CCC(O)C2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.5 %

Procedure:
To a solution of DL-3-pyrrolidinol (0.87 g, 10 mmol) in dichloromethane (10 ml) was added triethylamine (1.21 g, 12 mmol) and 4-butoxybezenesulfonyl chloride (2.69 g, 10.5 mmol). The mixture was stirred at room temperature for 2 h. It was then treated with 10 ml of saturated sodium carbonate solution for 18 h. The mixture was diluted with water, and the organic solvents were evaporated. The resulting suspension was filtered, and the precipitate was washed with water and hexanes, and dried to give 2.89 g of an off-white solid; m.p. 83-84° C.; MS (ES) m/z 299.9 (MH+); HRMS (CI) Calcd. for C14H22NO4S (MH+): 300.1269, Found: 300.1272.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=O)[CH2:10][CH2:9]1.Cl.[NH2:20][OH:21].[OH-].[Na+].Cl>C(O)C.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[N:20][OH:21])[CH2:10][CH2:9]1
Reactant: O=C1CCC(c2ccccc2F)c2ccccc21
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: ON=C1CCC(c2ccccc2F)c2ccccc21

Procedure:
32 g of 4-(2-fluorophenyl)-1-tetralone in 75 ml of ethanol are treated with a solution of 9.26 g of hydroxylamine hydrochloride in 10 ml of water and then with 17 g of powdered sodium hydroxide. The mixture is heated to boiling under reflux for 5 minutes, again cooled and then poured into a mixture of ice and dilute hydrochloric acid. The mixture is extracted with ether and the extract obtained is washed with water. After evaporation of the solvent, there is obtained 4-(2-fluorophenyl)-1-tetralone oxime of melting point 120°.
Reaction SMILES: [C:1]1(/[C:7](/[C:17]2[CH:22]=[CH:21][C:20]([CH:23]=[CH:24][C:25](O)=[O:26])=[CH:19][CH:18]=2)=[C:8](/[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)\[CH2:9][CH3:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+:28]([C:31]1[CH:32]=[C:33]([S:37]([NH2:40])(=[O:39])=[O:38])[CH:34]=[CH:35][CH:36]=1)([O-:30])=[O:29]>>[C:1]1([C:7]([C:17]2[CH:22]=[CH:21][C:20]([CH:23]=[CH:24][C:25]([NH:40][S:37]([C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([N+:28]([O-:30])=[O:29])[CH:32]=3)(=[O:38])=[O:39])=[O:26])=[CH:19][CH:18]=2)=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:9][CH3:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NS(=O)(=O)c1cccc([N+](=O)[O-])c1
Reactant: CC/C(=C(\c1ccccc1)c1ccc(C=CC(=O)O)cc1)c1ccccc1
Product: CCC(=C(c1ccccc1)c1ccc(C=CC(=O)NS(=O)(=O)c2cccc([N+](=O)[O-])c2)cc1)c1ccccc1

Procedure:
Prepared by coupling 1a and 3-nitrobenzenesulfonamide in accordance with Procedure 1, Method A described hereinabove. Yield (14%); 1H NMR (d6-DMSO) δ 8.59 (t, J=2.2 Hz, 1H), 8.47 (d, J=7.0 Hz, 1H), 8.30 (d, J=7.7 Hz, 1H) 7.87 (t, J=8.1 Hz, 1H), 7.38-7.07 (m, 13H), 6.83 (d, J=8.4 Hz, 2H), 6.38 (d, J=15.7 Hz, 1H), 2.35 (q, J=7.4 Hz, 2H), 0.81 (t, J=7.4 Hz, 3H); APcI m/z: 537 (M−H−).
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[NH:19][C:18](=[O:20])[C:17]([NH:21][C:22](=[O:31])[O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:16][CH:15]=1.[CH:32]1([CH2:35]Br)[CH2:34][CH2:33]1.O>CN(C)C=O>[Cl:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[N:19]([CH2:35][CH:32]2[CH2:34][CH2:33]2)[C:18](=[O:20])[C:17]([NH:21][C:22](=[O:31])[O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:16][CH:15]=1
Reactant: O=C(Nc1ccc(-c2ccccc2Cl)[nH]c1=O)OCc1ccccc1
Reactant: BrCC1CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(Nc1ccc(-c2ccccc2Cl)n(CC2CC2)c1=O)OCc1ccccc1
Reaction time: 4 h
Yield: 38.2 %

Procedure:
Cesium carbonate (1.07 g, 3.30 mmol) was added to a solution of benzyl 6-(2-chlorophenyl)-2-oxo-1,2-dihydropyridin-3-ylcarbamate (J. Med. Chem. 1994, 37, 3303-3312) (585 mg, 1.65 mmol) and cyclopropylmethyl bromide (0.19 mL, 1.98 mmol) in N,N-dimethylformamide (5 mL). After 4 h, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (2×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (hexanes→30% ethyl acetate/hexanes) gave the title compound (258 mg). MS 409.0 (M+1).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[CH:3]=1.[NH:13]1[CH2:18][CH2:17][CH:16]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH2:15][CH2:14]1>>[CH3:12][O:11][C:4]1[CH:3]=[C:2]([N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[CH2:15][CH2:14]2)[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9]
Reactant: C1CC(N2CCOCC2)CCN1
Reactant: COc1cc(F)ccc1[N+](=O)[O-]
Product: COc1cc(N2CCC(N3CCOCC3)CC2)ccc1[N+](=O)[O-]

Procedure:
The title compound was prepared according to the method described for Preparation 78 using 4-fluoro-2-methoxy-1-nitrobenzene and 4-(piperidin-4-yl)morpholine. The residue was purified using silica gel column chromatography eluting with 80-100% DCM in cyclohexanes.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[OH:12].CC(C)=O.C(=O)([O-])[O-].[K+].[K+].Br[CH2:24][C:25]#[N:26]>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:10])([F:11])[F:9])=[CH:4][C:3]=1[O:12][CH2:24][C:25]#[N:26]
Reactant: Oc1cc(C(F)(F)F)ccc1F
Reactant: N#CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: N#CCOc1cc(C(F)(F)F)ccc1F
Reaction time: 20 h

Procedure:
A solution of 2-fluoro-5-trifluoromethylphenol (25 g) in reagent grade acetone (0.55 L) is treated with solid potassium carbonate (7.7 g) followed by the rapid addition of neat bromoacetonitrile (10 mL). The heterogenous mixture is stirred vigorously for approximately 20 hours whereupon it is poured into water and extracted into diethyl ether. The combined ether extracts are washed with saturated sodium chloride and dried over anhydrous potassium carbonate. Filtration and concen-tration under reduced pressure gives a pale orange solid which is then chromatographed on silica gel, eluting with dichloromethane, to give the desired product as white solid (28.3 g).
Reaction SMILES: O[CH2:2][C@H:3]1[O:7][C:6](=[O:8])[N:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:4]1.C(N(CC)CC)C.[CH3:24][S:25](Cl)(=O)=O.C[S-].[Na+]>C(Cl)Cl.CN(C=O)C>[CH3:24][S:25][CH2:2][C@H:3]1[O:7][C:6](=[O:8])[N:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:4]1
Reactant: CC(C)(C)OC(=O)NN1C[C@@H](CO)OC1=O
Reactant: CS(=O)(=O)Cl
Agent: C[S-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CSC[C@@H]1CN(NC(=O)OC(C)(C)C)C(=O)O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 92 %

Procedure:
To a turbid solution of (S)-tert-butyl 5-(hydroxymethyl)-2-oxooxazolidin-3-ylcarbamate (800 mg, 3.44 mmol) in DCM (5 mL), triethylamine (436 mg, 4.31 mmol) and methanesulfonyl chloride (493 mg, 4.31 mmol) were added and the reaction was stirred, at r.t., under nitrogen for 1 h 30 min. Conversion into the corresponding methanesulfonyl intermediate was complete. The solution was washed with cold citric acid (pH=4-5) and cold brine and the organic layer was separated and dried over Na2SO4. Evaporation of the solvent at 32° C. yielded a colourless foam (980 mg; yield=92%) that was dissolved in DMF (5 mL). Sodium methanethiolate (302 mg, 4.31 mmol) was added and the mixture stirred at 60° C. for 1 h. Conversion into the title product was complete. AcOEt was added and the solution was washed with cold citric acid (pH=3-4), then cold water and cold brine. The organic layer was dried over Na2SO4 and the solvent evaporated, leaving the title compound as a yellow sticky solid that was crystallized from diisopropyl ether into a white solid (404 mg, 1.539 mg). Yield=45%.