Diisopropylcarbodiimide → HCID 57722719, compound

HRID 1987076Notes

Reaction equation

HRID 1987076 reaction equation
[Li].[C:2]([C:4]1[C:9]([CH2:10][C:11]([OH:13])=[O:12])=[C:8]([F:14])[C:7]([NH:15][CH2:16][C:17]([F:25])([F:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:6][CH:5]=1)#[N:3].[F:26][C:27]1[C:32](O)=[C:31]([F:34])[C:30]([F:35])=[C:29]([F:36])[C:28]=1[F:37].Cl.N1C=CC=CC=1.CN(C1C=CC=CN=1)C.C(N=C=NC(C)C)(C)C>CN(C)C=O.C(Cl)Cl>[F:26][C:27]1[C:32]([O:12][C:11](=[O:13])[CH2:10][C:9]2[C:4]([C:2]#[N:3])=[CH:5][CH:6]=[C:7]([NH:15][CH2:16][C:17]([F:25])([F:24])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:8]=2[F:14])=[C:31]([F:34])[C:30]([F:35])=[C:29]([F:36])[C:28]=1[F:37]

Participants

9

Reactant 6

HCID 12734DiisopropylcarbodiimideHCID 13041PentafluorophenolHCID 218852-DimethylaminopyridineHCID 3028194LithiumHCID 10176127Pyridinium chlorideHCID 68828084HCID 68828084, compound

Product 1

HCID 57722719HCID 57722719, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the lithium salt of [6-cyano-3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-fluoro-phenyl]-acetic acid (75 mg, 0.22 mmol), prepared essentially as described in Example 1k, in N,N-dimethylformamide (0.250 mL) and methylene chloride (0.750 mL) was added pentafluorophenol (121 mg, 0.66 mmol), pyridine hydrochloride (52 mg, 0.45 mmol), dimethylaminopyridine (14 mg, 0.11 mmol), and finally diisopropylcarbodiimide (0.038 mL, 0.24 mmol). The mixture was stirred at room temperature for 24 h. The solvents were evaporated under high vacuum and the residue was purified by flash column chromatography (20-30% ethyl acetate in hexanes) to yield the desired compound (51 mg, 50%). 1H-NMR (300 MHz, CDCl3) δ 8.68 (d, J=5.5 Hz, 1H), 7.84 (td, J=7.8 Hz, 1.7 Hz, 1H), 7.69 (dt, J=7.9 Hz, 1.1 Hz, 1H), 7.40-7.45 (m, 1H), 7.35 (dd, J=8.6 Hz, 1.3 Hz, 1H), 6.86 (t, J=8.5 Hz, 1H), 5.05 (br s, 1H), 4.12-4.23 (m, 4H). LC/MS (m/z) [M+1]+ 502.3 (calculated for C22H12F8N3O2, 502.3).

Workup

  1. customThe solvents were evaporated under high vacuum
  2. customthe residue was purified by flash column chromatography (20-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8ecef22cf16d497eae454bc21471072d
Source dataset
uspto-grants-2009_06
Patent number
US07550474B2

Reaction notes

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