Water → HCID 67432302, compound

HRID 237220Notes

Reaction equation

HRID 237220 reaction equation
[S:1]1[C:5]([C:6]2[C:7]([NH2:26])=[N:8][CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[CH:14][CH:13]=3)[N:11]=2)=[CH:4][CH:3]=[C:2]1[C:27]1[S:28][CH:29]=[CH:30][CH:31]=1.[Si:32]([O:39][C:40]1[CH:45]=[CH:44][C:43]([CH2:46][C:47](Cl)=[O:48])=[CH:42][CH:41]=1)([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].O>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[S:1]1[C:5]([C:6]2[C:7]([NH:26][C:47](=[O:48])[CH2:46][C:43]3[CH:42]=[CH:41][C:40]([O:39][Si:32]([C:35]([CH3:37])([CH3:36])[CH3:38])([CH3:33])[CH3:34])=[CH:45][CH:44]=3)=[N:8][CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[CH:14][CH:13]=3)[N:11]=2)=[CH:4][CH:3]=[C:2]1[C:27]1[S:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 3

HCID 962WaterHCID 121887072-[4-(Tert-butyldimethylsilyloxy)phenyl]acetyl chlorideHCID 67432716HCID 67432716, compound

Product 1

HCID 67432302HCID 67432302, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
50 °C

Procedure

Under an argon atmosphere, to a mixture of 3-(2,2′-bithiophen-5-yl)-5-[4-(tert-butyldimethylsilyloxy)phenyl]pyrazin-2-amine (7m) (350 mg, 752 μmol) and 4-(dimethylamino)pyridine (15.0 mg, 123 μmol) dissolved in anhydrous pyridine (15 mL) was added 2-[4-(tert-butyl dimethylsilyloxy)phenyl]acetyl chloride (10) prepared above at 0° C. and the mixture was heated with stirring at 50° C. for 20 hours. After cooling to room temperature, to this was added water and the product was extracted with ethyl acetate (100 mL×3). The combined organic extract was washed successively with water (200 mL) and brine (200 mL), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by column chromatography (silica gel 50 g, n-hexane/ethyl acetate=3/1) to give Compound 11m (298 mg, crude) as a brown oily substance. Rf=0.26 (n-hexane/ethyl acetate=3/1); 1H NMR (400 MHz, DMSO-d6) δ 0.16 (s, 6H), 0.22 (s, 6H), 0.92 (s, 9H), 0.94 (s, 9H), 3.64 (s, 2H), 6.76-6.85 (AA′BB′, 2H), 6.98-7.05 (AA′BB′, 2H), 7.06-7.13 (m, 2H), 7.19-7.27 (AA′BB′, 2H), 7.33 (d, 1H, J=3.6 Hz), 7.36 (d, 1H, J=3.6 Hz), 7.54-7.59 (m, 1H), 8.05-8.11 (AA′BB′, 2H), 8.91 (s, 1H), 10.65 (s, 1H).

Workup

  1. customprepared above at 0° C.
  2. temperaturethe mixture was heated
  3. temperatureAfter cooling to room temperature
  4. extractionthe product was extracted with ethyl acetate (100 mL×3)
  5. extractionThe combined organic extract
  6. washwas washed successively with water (200 mL) and brine (200 mL)
  7. dry with materialby drying over anhydrous sodium sulfate
  8. filtrationAfter filtration and concentration under reduced pressure
  9. customthe residue was purified by column chromatography (silica gel 50 g, n-hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-302a2af2afd24b5292bf67e48a4b9326
Source dataset
uspto-grants-2014_02
Patent number
US08642281B2

Reaction notes

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