Water → HCID 67433417, compound

HRID 237204Notes

Reaction equation

HRID 237204 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:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[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: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>[Si:32]([O:39][C:40]1[CH:41]=[CH:42][C:43]([CH2:46][C:47]([NH:21][C:18]2[C:17]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[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:48])=[CH:44][CH:45]=1)([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]

Participants

6

Reactant 3

HCID 962WaterHCID 121887072-[4-(Tert-butyldimethylsilyloxy)phenyl]acetyl chlorideHCID 67432963HCID 67432963, compound

Product 1

HCID 67433417HCID 67433417, compoundYield 58.2%

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-(naphthalen-2-yl)pyrazin-2-amine (7e) (500 mg, 1.17 mmol) and 4-(dimethylamino)pyridine (15.0 mg, 123 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 16 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 11e (460 mg, 681 μmol, 58.2%) as a yellow foamy solid. Rf=0.26 (n-hexane/diethyl ether=2/3); 1H NMR (400 MHz, DMSO-d6) δ 0.12 (s, 6H), 0.21 (s, 6H), 0.91 (s, 9H), 0.94 (s, 9H), 3.46 (s, 2H), 6.55-6.65 (AA′BB′, 2H), 6.91-6.97 (AA′BB′, 2H), 6.97-7.03 (AA′BB′, 2H), 7.47-7.58 (m, 2H), 7.75-8.00 (m, 4H), 8.08-8.14 (AA′BB′, 2H), 8.23 (s, 1H), 9.00 (s, 1H), 10.63 (s, 1H); 13C NMR (75.5 MHz, DMSO-d6) δ −4.6 (4C), 17.8, 17.9, 25.5 (6C), 119.4 (2C), 120.3 (2C), 125.5, 126.1, 126.6, 127.1, 127.2, 127.3, 127.5, 127.9, 128.2 (2C), 128.5, 130.2 (2C), 132.6, 132.8, 135.3, 137.6, 143.0, 147.5, 148.0, 153.7, 156.7, 169.4 (one carbon at the benzyl position was unobservable due to overlapping with the septet peak of DMSO); IR (KBr, cm−1) 478, 527, 687, 718, 746, 781, 804, 839, 914, 1009, 1082, 1103, 1128, 1169, 1261, 1362, 1415, 1445, 1472, 1508, 1605, 1670, 2857, 2886, 2928, 2955, 3057, 3221; HRMS (ESI+) m/z 698.3194 ([M+Na]+, C40H49N3NaO3Si2+ requires 698.3205).

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-7cd95200e9e44f12bacb368f6bedbc95
Source dataset
uspto-grants-2014_02
Patent number
US08642281B2

Reaction notes

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