Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[C:4]([CH3:15])[C:3]=1[C:16](=[O:18])[CH3:17].[Br-:19].[Br-:20].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC>C(#N)C>[Br:19][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6]2[CH:5]=[C:4]([CH3:15])[C:3]([C:16](=[O:18])[CH2:17][Br:20])=[C:2]([CH3:1])[CH:7]=2)=[CH:10][CH:11]=1
Reactant: [Br-]
Reactant: CC(=O)c1c(C)cc(Nc2ccccc2)cc1C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CC#N
Product: Cc1cc(Nc2ccc(Br)cc2)cc(C)c1C(=O)CBr
Temperature: 25 °C
Reaction time: 1 h
Yield: 57.6 %

Procedure:
To a solution of 1-(2,6-dimethyl-4-(phenylamino)phenyl)ethanone (2.10 g, 8.78 mmol) in acetonitrile (50 mL) was added tetrabutylammoniumtribromide (TBABr3, 4.24 g, 8.78 mmol). The reaction was stirred at room temperature for 60 min. The solution was concentrated under reduced pressure, added with water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous MgSO4(s), and concentrated under reduced pressure to give 1-(4-(4-bromophenylamino)-2,6-dimethylphenyl)-2-bromoethanone (2.01 g), which was used directly for the next step without further purification.
Reaction SMILES: [CH3:1][O:2][C@@H:3]1[C@H:7]([OH:8])[C@@H:6]([CH2:9][OH:10])[O:5][C@H:4]1[N:11]1[C:20]2[N:19]=[CH:18][N:17]=[C:15](N)[C:14]=2[N:13]=[CH:12]1.[N+]([O-])([O-])=[O:22].[Na+]>C(O)(=O)C>[CH3:1][O:2][C@@H:3]1[C@H:7]([OH:8])[C@@H:6]([CH2:9][OH:10])[O:5][C@H:4]1[N:11]1[C:20]2[N:19]=[CH:18][N:17]=[C:15]([OH:22])[C:14]=2[N:13]=[CH:12]1
Reactant: CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1cnc2c(N)ncnc21
Reactant: O=[N+]([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1cnc2c(O)ncnc21
Reaction time: 24 h

Procedure:
Deamination of 2'-O-methyladenosine was accomplished by a modified procedure of Iwai et al., Anomeric 9-D-Glucopyranosyl-adenines and 9-D-Glucopyranosyl-hypozanthines, in Synthetic Procedures in Nucleic Acid Chemistry 135-142 (Zorbach & Tipson eds., Interscience Publishers, New York, N.Y., 1965). To a solution of 2'-O-methyladenosine (6.61 g, 23.5 mmol) dissolved in 4.4% aqueous acetic acid was added 13.1 g sodium nitrate (190 mmol). This reaction solution was stirred 24 hours in a foil covered vessel and thereafter evaporated to dryness in vacuo. The product was desalted with Amberlite XAD-4 resin and recrystallized in methanol. FABMS (glycerol) m/z 284 (MH+).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:17][C@H:16]2[C@H:13]([CH2:14][NH:15]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:20](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O>[CH2:1]([O:8][C:9]([N:11]1[CH2:17][C@H:16]2[C@H:13]([CH2:14][N:15]2[CH3:20])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(OCc1ccccc1)N1C[C@H]2CN[C@H]2C1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C=O
Agent: [Na+]
Solvent: O
Product: CN1C[C@@H]2CN(C(=O)OCc3ccccc3)C[C@@H]21
Temperature: 25 °C
Yield: 90.4 %

Procedure:
To a solution of (1R,5R)-3,6-diazabicyclo[3.2.0]heptane-3-carboxylic acid benzyl ester (14.2 g, 61.2 mmol; prepared according to patent WO 2001081347) and aqueous formaldehyde (38%, 100 mL, 1.38 mol; Fisher) in water (100 mL) was added sodium triacetoxyborohydride (25.8 g, 122 mmol; Aldrich). The mixture was stirred at room temperature until the reaction was complete according to HPLC analysis. The mixture was extracted with chloroform (3×100 mL) and the organic phase was washed with brine (100 mL) and concentrated under reduced pressure to afford the title compound (13.6 g, 55.3 mmol; 90% yield): 1H NMR (300 MHz, CD3OD) δ ppm 7.26-7.42 (5H, m), 5.15 (2H, s), 3.85 (1H, dd, J=7, 4 Hz), 3.69-3.79 (1H, m), 3.42-3.55 (1H, m), 3.13-3.25 (4H, m), 2.98-3.09 (1H, m), 2.32 (3H, s); MS (DCI/NH3) m/z 247 (M+H)+.
Reaction SMILES: Cl[N:2]1[NH:6][CH:5]=[C:4]([C:7]2[N:8]([CH3:15])[C:9]([N+:12]([O-:14])=[O:13])=[CH:10][N:11]=2)[S:3]1.[CH:16]1([NH2:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>O1CCOCC1>[CH:16]1([NH:22][N:2]2[NH:6][CH:5]=[C:4]([C:7]3[N:8]([CH3:15])[C:9]([N+:12]([O-:14])=[O:13])=[CH:10][N:11]=3)[S:3]2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: Cn1c([N+](=O)[O-])cnc1C1=CNN(Cl)S1
Reactant: NC1CCCCC1
Solvent: C1COCCO1
Product: Cn1c([N+](=O)[O-])cnc1C1=CNN(NC2CCCCC2)S1

Procedure:
A mixture of 5.0 g. of 2-(2-chloro-5-thiadiazolyl)-1-methyl-5-nitroimidazole, 6.0 g. of cyclohexylamine and 125 ml. of dioxane is stirred at reflux until thin-layer chromatographic analysis indicates that the chloro intermediate is completely utilized. The dioxane is removed under reduced pressure and the residue triturated with aqueous sodium bicarbonate solution. Recrystallization from a mixture of ethylacetate and acetone yields the pure compound melting at 215°-217° C.
Reaction SMILES: [CH:1]1[C:10]2[C:11]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][C:12]=3[N:8]3[C:9]=2[C:4]([CH2:5][CH2:6][CH2:7]3)=[CH:3][C:2]=1[NH2:18].[C:19](Cl)(=[O:25])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>ClCCl>[CH:1]1[C:10]2[C:11]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][C:12]=3[N:8]3[C:9]=2[C:4]([CH2:5][CH2:6][CH2:7]3)=[CH:3][C:2]=1[NH:18][C:19](=[O:25])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CCCCCC(=O)Cl
Reactant: Nc1cc2c3c(c1)c1c(n3CCC2)CCCCC1
Solvent: ClCCl
Product: CCCCCC(=O)Nc1cc2c3c(c1)c1c(n3CCC2)CCCCC1
Yield: 82.7 %

Procedure:
Following the procedure in Example 1, Step 4, 5,6,9,10,11,12-hexahydro-4H,8H-cyclohepta[4,5]pyrrolo[3,2,1-ij]quinolin-2-amine (0.12 g, 0.50 mmol), hexanoyl chloride (0.072 mL, 0.52 mmol) and poly-(4-vinylpyridine) (700 mg) in dichloromethane (10 mL) provided 0.14 g of N-5,6,9,10,11,12-hexahydro-4H,8H-cyclohepta[4,5]pyrrolo[3,2,1-ij]quinolin-2-ylhexanamide. MS (ESI) m/z 339;
Reaction SMILES: [C:1]([C:6](=[CH:12][CH2:13][CH3:14])[C:7](=[O:11])[CH2:8][CH2:9][CH3:10])([O:3][CH2:4][CH3:5])=[O:2].BrN1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[CH3:14][C:13]1[O:11][C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([C:1]([O:3][CH2:4][CH3:5])=[O:2])[CH:12]=1
Reactant: CCC=C(C(=O)CCC)C(=O)OCC
Agent: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: CCCc1oc(C)cc1C(=O)OCC
Yield: 85.4 %

Procedure:
A mixture of 3.97 g (0.02 mole) 5-carboethoxy-5-octen-4-one and 3.56 g (0.02 mole) N-bromosuccinimide in 50 ml of carbon tetrachloride was heated at reflux for 12 hours. After cooling, the succinimide was removed by filtration and the solution concentrated by rotary evaporation. Distillation of the crude product gave 3.35 g (85%) of ethyl 5-methyl-2-propyl- 3-furoate, bp 104°-107° C. (9.5 mm).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][N:11]2[CH:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:14](=[O:24])[C:13]([C:25](=[O:56])[NH:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]4[CH:39]=[CH:38][N:37]=[C:36]([NH:40][CH:41]([C:48]5[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=5)[C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)[C:35]=4[Cl:54])=[C:29]([F:55])[CH:28]=3)=[CH:12]2)=[O:8])[CH2:3][CH2:2]1.C=O.[C:59](O)(=O)C.[BH3-]C#N.[Na+]>C(#N)C>[CH3:59][N:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][N:11]2[CH:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:14](=[O:24])[C:13]([C:25](=[O:56])[NH:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]4[CH:39]=[CH:38][N:37]=[C:36]([NH:40][CH:41]([C:48]5[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=5)[C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)[C:35]=4[Cl:54])=[C:29]([F:55])[CH:28]=3)=[CH:12]2)=[O:8])[CH2:3][CH2:2]1
Reactant: O=C(Nc1ccc(Oc2ccnc(NC(c3ccccc3)c3ccccc3)c2Cl)c(F)c1)c1cn(COC(=O)C2CCNCC2)cc(-c2ccc(F)cc2)c1=O
Reactant: CC(=O)O
Agent: C=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC#N
Product: CN1CCC(C(=O)OCn2cc(C(=O)Nc3ccc(Oc4ccnc(NC(c5ccccc5)c5ccccc5)c4Cl)c(F)c3)c(=O)c(-c3ccc(F)cc3)c2)CC1
Reaction time: 0.5 h

Procedure:
To a mixture of (3-(4-(2-(benzhydrylamino)-3-chloropyridin-4-yloxy)-3-fluorophenylcarbamoyl)-5-(4-fluorophenyl)-4-oxopyridin-1(4H)-yl)methyl piperidine-4-carboxylate (60 mg, 0.077 mmol), formaldehyde (37% in water, 0.08 mL, 0.077 mmol) and acetic acid (0.03 mL, 0.077) in acetonitrile (2 mL) at rt was added, NaCNBH3 (50 mg, 0.8 mmol). The resulting mixture was stirred for 30 min. The solvent was removed in vacuo and the crude product residue was used directly in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=O)[CH2:6][CH2:5]2.C(OC([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=O)(C)(C)C>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)[CH2:6][CH2:5]2
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=C1CCc2cc(Cl)ccc21
Product: Clc1ccc2c(c1)CCC2N1CCNCC1

Procedure:
The title compound was prepared in two steps by a standard reductive amination starting with 5-chloro-1-indanone and piperazine carboxylic acid tert-butyl ester followed by removal of the t-Boc group with HCl in 30% overall yield.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([NH2:17])[CH:14]=3)[NH:9]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[O:18]([C:25]1[CH:30]=[CH:29][C:28]([N:31]=[C:32]=[O:33])=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1COCC1>[O:18]([C:25]1[CH:26]=[CH:27][C:28]([NH:31][C:32]([NH:17][C:13]2[CH:14]=[C:15]3[C:16](=[CH:11][CH:12]=2)[N:8]([CH2:7][CH2:6][N:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[N:9]=[CH:10]3)=[O:33])=[CH:29][CH:30]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: Nc1ccc2c(c1)CN(CCN1CCCC1)N2
Reactant: O=C=Nc1ccc(Oc2ccccc2)cc1
Solvent: C1CCOC1
Product: O=C(Nc1ccc(Oc2ccccc2)cc1)Nc1ccc2c(cnn2CCN2CCCC2)c1
Temperature: 50 °C
Reaction time: 1 h

Procedure:
A mixture of 2-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-5-ylamine (0.100 g, 0.434 mmol) and 4-phenoxyphenyl isocyanate (0.0917 g, 0.434 mmol) in 6 mL of THF was stirred at 50° C. for 1 hour, cooled to room temperature and concentrated under reduced pressure. The residue was triturated in diethyl ether and collected by filtration to provide the title compound. 1H NMR (300 MHz, DMSO-D6) δ ppm 1.63 (m, 4 H), 2.44 (m, J=6.44 Hz, 4 H), 2.86 (t, J=6.61 Hz, 2 H), 4.46 (t, J=6.78 Hz, 2 H), 6.97 (m, 4 H), 7.09 (m, 1 H), 7.35 (m, 3 H), 7.49 (m, 2 H), 7.59 (m, 1 H), 7.88 (m, 1 H), 7.96 (s, 1 H), 8.65 (m, 2 H); MS (ESI) m/z 442 [M+H]+.
Reaction SMILES: Cl[C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1.[NH2:16][CH:17]([CH2:21][C:22]1[N:23]=[CH:24][N:25]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[C:30]([CH3:37])[CH:29]=2)[CH:26]=1)[C:18]([OH:20])=[O:19]>>[C:18]([CH:17]([NH:16][C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1)[CH2:21][C:22]1[N:23]=[CH:24][N:25]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[C:30]([CH3:37])[CH:29]=2)[CH:26]=1)([OH:20])=[O:19]
Reactant: Cc1cc(Cn2cnc(CC(N)C(=O)O)c2)ccc1[N+](=O)[O-]
Reactant: O=C(O)c1cc2cc(Cl)ccc2nc1Cl
Product: Cc1cc(Cn2cnc(CC(Nc3nc4ccc(Cl)cc4cc3C(=O)O)C(=O)O)c2)ccc1[N+](=O)[O-]

Procedure:
In close analogy to the procedure described in Example 32, 2,6-dichloroquinoline-3-carboxylic acid is reacted with 2-amino-3-[1-(3-methyl-4-nitro-benzyl)-1H-imidazol-4-yl]-propionic acid to provide the title compound in good yield. LCMS m/z 510 (M+1).
Reaction SMILES: Br[C:2]1[C:10]2[O:9][CH2:8][O:7][C:6]=2[CH:5]=[C:4]([CH2:11][CH:12]([CH3:14])[CH3:13])[CH:3]=1.[Li]CCCC.C([O:23][B:24](OC(C)C)[O:25]C(C)C)(C)C.Cl>C1COCC1.C(OCC)(=O)C>[CH2:11]([C:4]1[CH:3]=[C:2]([B:24]([OH:25])[OH:23])[C:10]2[O:9][CH2:8][O:7][C:6]=2[CH:5]=1)[CH:12]([CH3:14])[CH3:13]
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: CC(C)Cc1cc(Br)c2c(c1)OCO2
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)Cc1cc2c(c(B(O)O)c1)OCO2
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 55 %

Procedure:
To a mixture of 4-bromo-6-isobutyl-benzo[1,3]dioxole (232 mg, 0.90 mmol) in THF (3 mL) cooled to −78° C. under an atmosphere of argon was added n-BuLi (0.72 mL, 2.5 M, 1.80 mmol) dropwise. The reaction mixture was stirred for 5 minutes and triisopropylborate (0.62 mL, 2.71 mmol) was added dropwise. The mixture was stirred at −50° C. for 2 hours then warmed up to room temperature and stirred overnight at room temperature. 2.0 N HCl was slowly added to the reaction mixture. After 30 minutes the mixture was diluted with ethyl acetate and the layers separated. The organic layer was further washed with water, brine, dried (MgSO4), filtered and evaporated. The residue was chromatographed on silica gel (30% ethyl acetate in hexane) to give 110 mg of 6-isobutyl-benzo[1,3]dioxole-4-boronic acid (55%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]=[CH:10][C@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16]([O:23][NH2:24])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:16]([O:23][NH:24][C:13]([C@@H:9]1[CH:10]=[CH:11][CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:15])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CC(C)(C)OC(=O)N1CC=C[C@H]1C(=O)O
Reactant: NOCc1ccccc1
Product: CC(C)(C)OC(=O)N1CC=C[C@H]1C(=O)NOCc1ccccc1

Procedure:
(S)-tert-Butyl 2-(benzyloxycarbamoyl)-2,5-dihydro-1H-pyrrole-1-carboxylate is prepared from (S)-1-(tert-butoxycarbonyl)-2,5-dihydro-1H-pyrrole-2-carboxylic acid (Boc-3,4-dehydro-proline) and O-benzylhydroxylamine following Method G. 1H NMR (300 MHz, CHCl3) δ 9.38 (s, 0.5H), 8.46 (s, 0.5H), 7.52-7.22 (m, 5H), 6.01-5.77 (m, 2H), 5.04-4.79 (m, 3H), 4.38-3.99 (m, 2H), 1.43 (s, 9).
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[C:5](=[O:11])[NH:6][C:7](=[O:10])[NH:8][CH:9]=1.[CH2:12](Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[CH2:12]([N:8]1[CH:9]=[C:4]([CH2:3][O:2][CH3:1])[C:5](=[O:11])[NH:6][C:7]1=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: BrCc1ccccc1
Reactant: COCc1c[nH]c(=O)[nH]c1=O
Product: COCc1cn(Cc2ccccc2)c(=O)[nH]c1=O

Procedure:
substituting 5-methoxymethyl-2,4(1H,3H)-pyrimidinedione and benzyl bromide gave 1-benzyl-5-methoxymethyl-2,4(1H,3H)-pyrimidinedione, m.p. 134°-136° C.;
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([NH:9][CH2:10][C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][C:20]=2[F:21])[N:17]=[CH:16][CH:15]=[CH:14]3)[C:5]([NH2:8])=[N:6][CH:7]=1.[N:22]([O-])=O.[Na+]>C(O)(=O)C.O>[Br:1][C:2]1[N:3]=[C:4]2[N:9]([CH2:10][C:11]3[CH:12]=[C:13]4[C:18](=[CH:19][C:20]=3[F:21])[N:17]=[CH:16][CH:15]=[CH:14]4)[N:22]=[N:8][C:5]2=[N:6][CH:7]=1
Reactant: O=N[O-]
Reactant: Nc1ncc(Br)nc1NCc1cc2cccnc2cc1F
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Fc1cc2ncccc2cc1Cn1nnc2ncc(Br)nc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 61 %

Procedure:
To a solution of 5-bromo-N*3*-(7-fluoro-quinolin-6-ylmethyl)-pyrazine-2,3-diamine (90 mg, 0.26 mmol) in acetic acid (4 mL) was added a solution of sodium nitrite (11.4 mg, 0.26 mmol) in water (1 mL). After stirring at rt for 3 h, the solvent was removed in vacuo. The residue was diluted with NaHCO3 (aq.), extracted with DCM. The organic layer was separated and washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography with DCM:MeOH=50:1 to give the title compound as a yellow solid (57.0 mg, 61%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 9.03 (s, 1H), 8.94 (d, 1H), 8.40 (d, 1H), 8.08 (d, 1H), 7.84 (d, 1H), 7.55 (dd, 1H), 7.53 (dd, 1H), 6.21 (s, 2H). LCMS (method A): [MH]+=359/361, tR=2.23 min.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:12]C(=O)[NH:10][CH:9]2[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])[CH:16]=2)=[CH:4][CH:3]=1.[OH-].[Na+]>C(O)C>[NH2:10][CH:9]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C:23]([F:26])([F:24])[F:25])[CH:16]=1)[CH:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[OH:12]
Reactant: O=C1NC(Cc2cccc(OCC(F)(F)F)c2)C(c2ccc(F)cc2)O1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: NC(Cc1cccc(OCC(F)(F)F)c1)C(O)c1ccc(F)cc1
Yield: 81.8 %

Procedure:
To a solution of (4RS,5SR)-5-(4-fluorophenyl)-4-((3-(2,2,2-trifluoroethoxy)phenyl)methyl)-1,3-oxazolidin-2-one (1.2 g, 3.25 mmol) in ethanol (10 ml) was added 8N aqueous sodium hydroxide solution (2.0 ml, 16 mmol) and the mixture was heated under reflux for 2 hrs. The reaction solution was concentrated, diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give (1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-(3-(2,2,2-trifluoroethoxy)phenyl)-1-propanol (913 mg, 82%).
Reaction SMILES: Cl.Cl.[CH3:3][NH:4][NH:5][CH3:6].[CH3:7][S:8](Cl)(=[O:10])=[O:9].Cl>>[CH3:7][S:8]([N:4]([CH3:3])[N:5]([S:8]([CH3:7])(=[O:10])=[O:9])[CH3:6])(=[O:10])=[O:9]
Reactant: CNNC
Reactant: CS(=O)(=O)Cl
Agent: Cl
Product: CN(N(C)S(C)(=O)=O)S(C)(=O)=O
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 32.4 %

Procedure:
1,2-Dimethylhydrazine dihydrochloride (2.6 g, 0.02 mol) was suspended in ice-cold dry pyridine (6 ml) and the mixture was stirred for 10 minutes. Methanesulfonyl chloride (5.0 g, 0.043 mol) was added in portions to this mixture, while maintaining the temperature between 0° and 10° C. After an additional 1 hour of stirring at 0° to 5° C., the reaction mixture was left in a freezer (-10° C.) overnight. The pH of the reaction mixture was adjusted to pH 1 with cold dilute hydrochloric acid. The solid that separated was filtered and recrystallized from ethanol (Norit A) to give 1.4 g (32%) of the title compound: m.p. 168°-169° C.; anal. (C4H12N2O4S2) C,H,N; 1H NMR (CDCl3) δ 3.1 [2s, 12H, 2(CH3SO2NCH3)].
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]2[CH:13]=[C:14]([CH:16]=[O:17])[N:15]=[C:5]2[CH:4]=1.O>O1CCCC1>[CH2:3]([C:12]1[CH:7]=[CH:8][C:9]([CH:16]([C:14]2[N:15]=[C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:12]4[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=4)[N:6]3[CH:13]=2)[OH:17])=[CH:10][CH:11]=1)[CH3:4]
Reactant: COc1cc2nc(C=O)cn2c2ccccc12
Solvent: C1CCOC1
Solvent: O
Product: CCc1ccc(C(O)c2cn3c(cc(OC)c4ccccc43)n2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 127.6 %

Procedure:
2.78 g (15 mmol) of p-bromo-ethylbenzene were added dropwise to a stirred suspension of 0.36 g (15 mg-atoms) of magnesium turnings in 25 ml of anhydrous tetrahydrofuran containing an iodine crystal to form a Grignard reagent and the resulting solution was added dropwise to a suspension of 2.26 g (10 mmol) of the product of Step B in 50 ml of anhydrous tetrahydrofuran. The mixture was stirred at room temperature for one hour and was poured into 200 ml of water. The mixture was extracted with 200 ml of chloroform and was filtered through a celite pad. The separated aqueous phase was extracted twice with 100 ml of chloroform and the combined organic phases were dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure to obtain a green gum. The latter was chromatographed over 200 g of silica gel and was eluted with a 95-5 chloroform-methanol mixture to obtain 2.12 g (64% yield) of (4-ethyl-phenyl)(5-methoxy-imidazo[1,2-a] quinolin-2-yl)-methanol in the form of a green gum.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[C:6](Cl)(=[O:12])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].Cl>O>[C:6]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)(=[O:12])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: c1ccsc1
Reactant: CCCCCC(=O)Cl
Agent: Cl
Solvent: O
Product: CCCCCC(=O)c1cccs1
Temperature: 0 °C
Reaction time: 8 h
Yield: 94 %

Procedure:
The 2-hexanoyl thiophene was prepared by dissolving thiophene (0.9 g, 10.7 mmol) and hexanoyl chloride (1.52 g, 11.3 mmol), both of which were obtained from Aldrich Chemical Supply and used without further purification, in benzene (20 mL). The solution was cooled to 0° C. under argon. Stannic chloride (10.7 mL, 10.7 mmol, 1M solution in dichloromethane) was added dropwise and the resulting solution was stirred overnight. The next day, 20 mL of a 50:50 mixture of concentrated hydrochloric acid and water was added. The resulting mixture was stirred for two hours whereupon the color became golden yellow. The organic layer was separated, washed with sodium bicarbonate solution, dried (Na2 SO4) and concentrated to yield 2-hexanoyl thiophene (94% yield). The compound was further purified by column chromatography using hexane/dichloromethane as the elutant.
Reaction SMILES: [CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCCC1.[CH2:21]([O:23][C:24](=[O:29])[C:25](Br)([CH3:27])[CH3:26])[CH3:22]>O>[CH2:21]([O:23][C:24](=[O:29])[C:25]([O:15][C:12]1[CH:13]=[N:14][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:10][CH:11]=1)([CH3:27])[CH3:26])[CH3:22]
Reactant: CCOC(=O)C(C)(C)Br
Reactant: Oc1ccc(OCc2ccccc2)nc1
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)C(C)(C)Oc1ccc(OCc2ccccc2)nc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 38 %

Procedure:
To an ice-cold solution of 0.5 g (2.48 mmol) 6-benzyloxy-3-hydroxypyridine (commercially available) in 5 mL tetrahydrofuran 0.12 g (2.7 mmol) sodium hydride (55% dispersion in mineral oil) was added in portions. After the vigorous gas evolution had ceased the reaction mixture was stirred for another 20 min., then 0.44 mL (3.0 mmol) ethyl-alpha-bromoisobutyrate (commercially available) were added dropwise. The light brown suspension was stirred for 23 h at room temperature and then poured into water. The aqueous phase was extracted three times with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate and filtered. Silica gel was added to the filtrate and the slurry evaporated. The resulting solid is purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane:ethyl acetate (100:0 to 70:30) to give the product as a colorless oil (38%). MS (Turbo Spray): m/z=316.1 [M+H].
Reaction SMILES: [O-]CC.[K+:4].[C:5]([O:12][CH2:13][CH3:14])(=[O:11])[C:6]([O:8]CC)=O.[CH2:15]([N:22]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:23]1[C:28]([N+:29]([O-:31])=[O:30])=[C:27]([CH3:32])[CH:26]=[CH:25][N:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(OCC)C>[CH2:33]([N:22]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:23]1[C:28]([N+:29]([O-:31])=[O:30])=[C:27](/[CH:32]=[C:6](\[O-:8])/[C:5]([O:12][CH2:13][CH3:14])=[O:11])[CH:26]=[CH:25][N:24]=1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1.[K+:4]
Reactant: CCOC(=O)C(=O)OCC
Reactant: Cc1ccnc(N(Cc2ccccc2)Cc2ccccc2)c1[N+](=O)[O-]
Agent: CC[O-]
Agent: [K+]
Solvent: CCOCC
Product: CCOC(=O)/C([O-])=C/c1ccnc(N(Cc2ccccc2)Cc2ccccc2)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 75.9 %

Procedure:
A slurry of potassium ethoxide (391 mg, 4.64 mmol) in diethyl ether (4 mL) under N2 was cooled to 0° C. under vigorous stirring. Diethyl oxalate (0.63 mL, 4.65 mmol) was added, and the mixture was stirred for 5 min. A solution of 2-(dibenzylamino)-4-methyl-3-nitropyridine (1.52 g, 4.56 mmol) in diethyl ether (3 mL) was added, and the mixture was stirred for 16 h while slowly warming to room temperature, during which time a precipitate formed. The solid was collected on a sintered glass frit and rinsed several times with additional diethyl ether. The solid was transferred to a vial and dried under vacuum at 30° C. for 2 h to provide potassium (1Z)-1-[2-(dibenzylamino)-3-nitropyridin-4-yl]-3-ethoxy-3-oxoprop-1-en-2-olate (1.63 g, 3.46 mmol, 76%) as a light orange solid. This product was immediately used without purification or identification.