Ethyl Acetate → HCID 178518571, compound

HRID 1914892Notes

Reaction equation

HRID 1914892 reaction equation
[F:1][C:2]1[C:10]2[N:11]([C:15]3[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=3[F:22])[C:12](=[O:14])[NH:13][C:9]=2[C:8]2[O:7][CH:6]=[CH:5][C:4]=2[C:3]=1[F:23].[CH:24]1([S:27](Cl)(=[O:29])=[O:28])[CH2:26][CH2:25]1.C(OCC)(=O)C>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCCCCC>[CH:24]1([S:27]([IH:21][C:18]2[CH:19]=[CH:20][C:15]([N:11]3[C:10]4[C:2]([F:1])=[C:3]([F:23])[C:4]5[CH:5]=[CH:6][O:7][C:8]=5[C:9]=4[NH:13][C:12]3=[O:14])=[C:16]([F:22])[CH:17]=2)(=[O:29])=[O:28])[CH2:26][CH2:25]1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 2760919Cyclopropanesulfonyl chlorideHCID 672379484,5-Difluoro-3-(2-fluoro-4-iodophenyl)-1H-benzofuro[6,7-d]imidazol-2(3H)-one

Product 1

HCID 178518571HCID 178518571, compoundYield 50.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Conditions

Temperature
30 °C

Procedure

TEA (0.062 mL, 0.4465 mmol) was added to a solution of 4,5-difluoro-3-(2-fluoro-4-iodophenyl)-1H-benzofuro[6,7-d]imidazol-2(3H)-one (I-32a: 0.064 g, 0.1488 mmol) in dry DCM (5 mL) at 0° C. This was followed by the addition of cyclopropanesulfonyl chloride (0.0331 g, 0.222 mmol) and catalytic amount of DMAP. The reaction mass was stirred for 3 hours at 20-40° C. The reaction was monitored by TLC (25% ethyl acetate in hexane). The reaction mass was concentrated under reduced pressure and the concentrate was extracted with ethyl acetate. The organic layer was washed with water, brine solution, dried over sodium sulphate and concentrated under reduced pressure to afford the crude compound. Purification by column chromatography on silica gel (20% ethyl acetate in hexane) afforded 40 mg of the product (50% yield). 1H NMR (CDCl3, 300 MHz): δ 7.77 (t, 2H), 7.65 (d, 1H), 7.29 (d, 1H), 6.99 (d, 1H), 3.31-3.38 (m, 1H), 1.62-1.74 (dd, 2H), 1.23-1.30 (m, 2H). LCMS: 93.99%, m/z=534.6 (M+1). HPLC: 96.34%

Workup

  1. concentrationThe reaction mass was concentrated under reduced pressure
  2. extractionthe concentrate was extracted with ethyl acetate
  3. washThe organic layer was washed with water, brine solution
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude compound
  7. customPurification by column chromatography on silica gel (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8d9d9a0ce7b74f0f825a7b2becd934b4
Source dataset
uspto-grants-2013_12
Patent number
US08614239B2

Reaction notes

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