Water → 2-[4-(tert-Butyldimethylsilyloxy)phenyl]-N-{5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-phenylpyrazin-2-yl}acetamide

HRID 237196Notes

Reaction equation

HRID 237196 reaction equation
[Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[C:17]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:18]([NH2:21])=[N:19][CH:20]=2)=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si:28]([O:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42][C:43](Cl)=[O:44])=[CH:38][CH:37]=1)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29].O>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[Si:28]([O:35][C:36]1[CH:37]=[CH:38][C:39]([CH2:42][C:43]([NH:21][C:18]2[C:17]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:16][C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])=[CH:14][CH:13]=3)=[CH:20][N:19]=2)=[O:44])=[CH:40][CH:41]=1)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]

Participants

6

Reactant 3

HCID 962WaterHCID 121205005-[4-(tert-Butyldimethylsilyloxy)phenyl]-3-phenylpyrazin-2-amineHCID 121887072-[4-(Tert-butyldimethylsilyloxy)phenyl]acetyl chloride

Product 1

HCID 674309822-[4-(tert-Butyldimethylsilyloxy)phenyl]-N-{5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-phenylpyrazin-2-yl}acetamideYield 75.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
50 °C

Procedure

Under an argon atmosphere, to a mixture of 5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-phenylpyrazin-2-amine (7a) (504 mg, 1.33 mmol) and 4-(dimethylamino)pyridine (16.3 mg, 133 μmol) dissolved in anhydrous pyridine (20 mL) was added 2-[4-(tert-butyldimethylsilyloxy)phenyl]acetyl chloride (10) prepared above at 0° C. and the mixture was heated with stirring at 50° C. for 18 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=4/1) to give Compound 11a (630 mg, 1.01 mmol, 75.4%) as a yellow foamy solid. Rf=0.33 (n-hexane/diethyl ether=2/3); 1H NMR (400 MHz, DMSO-d6) δ 0.18 (s, 6H), 0.23 (s, 6H), 0.94 (s, 9H), 0.96 (s, 9H), 3.47 (s, 2H), 6.72-6.79 (AA′BB′, 2H), 6.96-7.02 (AA′BB′, 2H), 7.03-7.09 (AA′BB′, 2H), 7.29-7.39 (m, 3H), 7.66-7.74 (m, 2H), 8.05-8.12 (AA′BB′, 2H), 8.98 (s, 1H), 10.54 (s, 1H); 13C NMR (75.5 MHz, DMSO-d6) δ −4.6 (4C), 17.9, 18.0, 25.50 (3C), 25.54 (3C), 41.7, 119.5 (2C), 120.3 (2C), 127.8 (2C), 127.9, 128.0 (2C), 128.2 (2C), 128.5, 128.9, 130.3 (2C), 130.5, 137.6, 142.8, 147.6, 148.0, 153.8, 156.7, 169.3; IR (KBr, cm−1) 523, 694, 781, 804, 839, 914, 1020, 1070, 1086, 1105, 1169, 1263, 1371, 1416, 1510, 1605, 1672, 2857, 2886, 2930, 2955, 3040, 3059, 3233; HRMS (ESI+)/z 648.3043 ([M+Na]+, C36H47N3NaO3Si2+ requires 648.3048).

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=4/1)

Sources & evidence

ORD record
ord-61044d6159ba4965b7d10fed0fb05c85
Source dataset
uspto-grants-2014_02
Patent number
US08642281B2

Reaction notes

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