Sodium Chloride → HCID 86689178, compound

HRID 1467385Notes

Reaction equation

HRID 1467385 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]1[C:22]2[C:21]3[CH:20]=[C:19]([OH:23])[C:18]([O:24][CH3:25])=[CH:17][C:16]=3[N:15]=[CH:14][C:13]=2[N:12]([CH3:26])[C:11]1=[O:27])[C:5]#[N:6].C1(P(C2C=CC=CC=2)C2C=CC=CN=2)C=CC=CC=1.[CH3:47][Si:48]([CH3:64])([CH3:63])[CH2:49][CH2:50][O:51][C:52](=[O:62])[NH:53][CH2:54][CH:55](O)[C:56]1[S:57][CH:58]=[CH:59][CH:60]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C>[C:5]([C:4]1[CH:7]=[CH:8][C:9]([N:10]2[C:22]3[C:21]4[CH:20]=[C:19]([O:23][CH:55]([C:56]5[S:57][CH:58]=[CH:59][CH:60]=5)[CH2:54][NH:53][C:52](=[O:62])[O:51][CH2:50][CH2:49][Si:48]([CH3:64])([CH3:47])[CH3:63])[C:18]([O:24][CH3:25])=[CH:17][C:16]=4[N:15]=[CH:14][C:13]=3[N:12]([CH3:26])[C:11]2=[O:27])=[C:2]([F:1])[CH:3]=1)#[N:6]

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 6218932-PyridyldiphenylphosphineHCID 66611737HCID 66611737, compoundHCID 77230781HCID 77230781, compound

Product 1

HCID 86689178HCID 86689178, compoundYield 41.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Fluoro-4-(8-hydroxy-7-methoxy-3-methyl-2-oxo-2,3-dihydroimidazo[4,5-c]quinolin-1-yl)benzonitrile (350 mg, 961 μmol) and diphenyl-2-pyridylphosphine (1.46 g, 5.39 mmol) were dissolved in tetrahydrofuran (105 ml). 2-Trimethylsilanylethyl(2-hydroxy-2-thiophen-2-ylethyl)carbamate (787 mg, 2.74 mmol) and diisopropyl azodicarboxylate (788 μl, 4.01 mmol) were subsequently added. The reaction mixture was stirred at room temperature for 15 min. When the reaction was complete (HPLC-MS), it was added to ethyl acetate (50 ml) and saturated sodium chloride solution (50 ml) and extracted. The aqueous phase was extracted with further ethyl acetate (25 ml). The combined organic phases were washed with water (25 ml), dried over Na2SO4 and filtered. The filtrate was evaporated to dryness in vacuo, and the residue was chromatographed over flash silica gel (solvent gradient ethyl acetate/0-7% by vol. of ethanol), giving 2-trimethylsilanylethyl {2-[1-(4-cyano-2-fluorophenyl)-7-methoxy-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-8-yloxy]-2-thiophen-2-ylethyl}carbamate (253 mg, 399 μmol) as solid. MS: 634.2 (M+H+), TLC (HPTLC): Rf=0.34 (ethyl acetate/ethanol 8:1, parts by volume).

Workup

  1. extractionextracted
  2. extractionThe aqueous phase was extracted with further ethyl acetate (25 ml)
  3. washThe combined organic phases were washed with water (25 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness in vacuo
  7. customthe residue was chromatographed over flash silica gel (solvent gradient ethyl acetate/0-7% by vol. of ethanol)

Sources & evidence

ORD record
ord-b79a2b37e962425ca0321506f0d57204
Source dataset
uspto-grants-2015_04
Patent number
US09000153B2

Reaction notes

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