Water → HCID 67432760, compound

HRID 333605Notes

Reaction equation

HRID 333605 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][C:3]2[CH:27]=[CH:28][CH:29]=[CH:30][C:2]1=2.[Si:31]([O:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:45][C:46](Cl)=[O:47])=[CH:41][CH:40]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].O>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[S:1]1[C:5]([C:6]2[C:7]([NH:26][C:46](=[O:47])[CH2:45][C:42]3[CH:41]=[CH:40][C:39]([O:38][Si:31]([C:34]([CH3:36])([CH3:35])[CH3:37])([CH3:32])[CH3:33])=[CH:44][CH:43]=3)=[N:8][CH:9]=[C:10]([C:12]3[CH:13]=[CH:14][C:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[CH:16][CH:17]=3)[N:11]=2)=[CH:4][C:3]2[CH:27]=[CH:28][CH:29]=[CH:30][C:2]1=2

Participants

6

Reactant 3

HCID 962WaterHCID 121887072-[4-(Tert-butyldimethylsilyloxy)phenyl]acetyl chlorideHCID 67431842HCID 67431842, compound

Product 1

HCID 67432760HCID 67432760, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
50 °C

Procedure

Under an argon atmosphere, to a mixture of 3-(benzo[b]thiophen-2-yl)-5-[4-(tert-butyldimethylsilyloxy)phenyl]pyrazin-2-amine (7h) (505 mg, 1.16 mmol) and 4-(dimethylamino)pyridine (15.0 mg, 123 μmol) dissolved in anhydrous pyridine (20 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 15 hours. After cooling to room temperature, to this was added water and the product was extracted with ethyl acetate (200 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). The resulting solid was recrystallized (n-hexane/ethanol) to give Compound 11h (294 mg, 431 μmol, 37.0%) as a colorless solid. Rf=0.19 (n-hexane/diethyl ether=2/3); 1H NMR (400 MHz, DMSO-d6) δ 0.19 (s, 6H), 0.25 (s, 6H), 0.96 (s, 9H), 0.97 (s, 9H), 3.71 (s, 2H), 6.82-6.89 (AA′BB′, 2H), 7.01-7.08 (AA′BB′, 2H), 7.26-7.42 (m, 4H, includes AA′BB′), 7.60-7.65 (m, 2H), 7.96 (d, 1H, J=7.9 Hz), 8.10-8.18 (AA′BB′, 2H), 9.02 (s, 1H), 10.82 (s, 1H), IR (KBr, cm−1) 525, 677, 692, 710, 727, 743, 779, 797, 808, 835, 922, 972, 1011, 1074, 1171, 1256, 1327, 1362, 1391, 1416, 1445, 1503, 1603, 1657, 859, 2886, 2930, 2957, 3059, 3161, 3211; HRMS (ESI+) m/z 704.2758 ([M+Na]+, C38H47N3NaO3SSi2+ requires 704.2769).

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 (200 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)
  10. customThe resulting solid was recrystallized (n-hexane/ethanol)

Sources & evidence

ORD record
ord-e7cac050d34646e19653d0e5ee71bca8
Source dataset
uspto-grants-2014_11
Patent number
US08883432B2

Reaction notes

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