Water → HCID 67431415, compound

HRID 1522666Notes

Reaction equation

HRID 1522666 reaction equation
[S:1]1[CH:5]=[C:4]([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)[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[CH:5]=[C:4]([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)[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 67430166HCID 67430166, compound

Product 1

HCID 67431415HCID 67431415, compoundYield 63.5%

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-3-yl)-5-[4-(tert-butyldimethylsilyloxy)phenyl]pyrazin-2-amine (7i) (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) to give Compound 11i (505 mg, 740 μmol, 63.5%) as a yellow solid. Rf=0.19 (n-hexane/diethyl ether=2/3); 1H NMR (400 MHz, DMSO-d6) δ 0.15 (s, 6H), 0.20 (s, 6H), 0.91 (s, 9H), 0.93 (s, 9H), 3.41 (s, 2H), 6.65-6.71 (AA′BB′, 2H), 6.93-7.00 (2AA′BB′, 4H), 7.35-7.42 (m, 2H), 7.80 (s, 1H), 7.95-8.07 (m, 4H, includes AA′BB′), 9.01 (s, 1H), 10.49 (s, 1H); 13C NMR (75.5 MHz, DMSO-d6) δ −4.5 (4C), 17.89, 17.93, 25.47 (3C), 25.54 (3C), 41.6, 119.5 (2C), 120.4 (2C), 122.6, 123.5, 124.4 (2C), 127.3, 127.9, 128.1 (2C), 128.9, 130.3 (2C), 132.3, 137.5, 137.5, 139.4, 143.7, 143.8, 147.6, 153.8, 156.7, 169.4; IR (KBr, cm−1) 683, 700, 735, 758, 781, 804, 839, 914, 1169, 1261, 1331, 1362, 1435, 1472, 1508, 1605, 1670, 2857, 2886, 2930, 2955; HRMS (ESI+) m/z 704.2781 ([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)

Sources & evidence

ORD record
ord-28e8840ecd164475aeb28eb3bef49250
Source dataset
uspto-grants-2015_07
Patent number
US09075058B2

Reaction notes

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