Ammonium Chloride → 2-(4-Hydroxyphenyl)-N-[5-(4-hydroxyphenyl)-3-(naphthalen-1-yl)pyrazin-2-yl]acetamide

HRID 1522659Notes

Reaction equation

HRID 1522659 reaction equation
[Si]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([NH:18][C:19]2[C:24]([C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=[CH:27][CH:26]=3)=[N:23][C:22]([C:35]3[CH:40]=[CH:39][C:38]([O:41][Si](C(C)(C)C)(C)C)=[CH:37][CH:36]=3)=[CH:21][N:20]=2)=[O:17])=[CH:11][CH:10]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[NH4+].[Cl-]>C1COCC1>[OH:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([NH:18][C:19]2[C:24]([C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=[CH:27][CH:26]=3)=[N:23][C:22]([C:35]3[CH:36]=[CH:37][C:38]([OH:41])=[CH:39][CH:40]=3)=[CH:21][N:20]=2)=[O:17])=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 674319522-[4-(tert-Butyldimethylsilyloxy)phenyl]-N-[5-{4-(tert-butyldimethyl silyloxy)phenyl}-3-(naphthalen-1-yl)pyrazin-2-yl]acetamide

Product 1

HCID 1359802472-(4-Hydroxyphenyl)-N-[5-(4-hydroxyphenyl)-3-(naphthalen-1-yl)pyrazin-2-yl]acetamideYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-[4-(tert-butyldimethylsilyloxy)phenyl]-N-[5-{4-(tert-butyldimethylsilyloxy)phenyl}-3-(naphthalen-1-yl)pyrazin-2-yl]acetamide (11d) (291 mg, 430 μmol) in THF (5 mL) was added tetrabutylammonium fluoride (1.0 M THF solution) (2.20 mL, 2.20 mmol) at 0° C. and the mixture was stirred for 30 minutes while elevating to room temperature. To the mixture was added saturated NH4Cl aqueous solution (50 mL) and the product was extracted with ethyl acetate (100 mL×3). The combined organic extract was washed successively with saturated NH4Cl aqueous solution (200 mL), water (200 mL) and brine (200 mL), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was recrystallized (n-hexane/ethanol) to give Compound 4d (TMD-338) (181 mg, 404 μmol, 93.8%) as a brown solid. Rf=0.56 (dichloromethane/methanol=9/1); HPLC retention time 9.1 min; 1H NMR (400 MHz, DMSO-d6) δ 3.17 (s, 2H), 6.45-6.53 (AA′BB′, 2H), 6.56-6.64 (AA′BB′, 2H), 6.80-6.88 (AA′BB′, 2H), 7.35-7.56 (m, 4H), 7.61-7.68 (m, 1H), 7.88-8.04 (m, 4H, includes AA′BB′), 9.03 (s, 1l), 9.15 (s, 1H), 9.85 (s, 1H), 10.14 (s, 1H); 13C NMR (75.5 MHz, DMSO-d6) δ 41.2, 115.0 (2C), 115.9 (2C), 125.1, 125.3, 125.4, 125.8, 126.3, 126.5, 126.9, 128.25, 128.27 (2C), 128.7, 129.8 (2C), 130.7, 133.4, 134.9, 138.0, 144.0, 148.38, 148.44, 155.9, 159.2, 169.8; IR (KBr, cm−1) 492, 540, 623, 777, 802, 839, 982, 1078, 1171, 1231, 1317, 1364, 1447, 1477, 1516, 1609, 1670, 3055, 3246; HRMS (ESI+) m/z 470.1483 ([M+Na]+, C28H21N3NaO3+ requires 470.1475).

Workup

  1. customwhile elevating to room temperature
  2. extractionthe product was extracted with ethyl acetate (100 mL×3)
  3. extractionThe combined organic extract
  4. washwas washed successively with saturated NH4Cl aqueous solution (200 mL), water (200 mL) and brine (200 mL)
  5. dry with materialby drying over anhydrous sodium sulfate
  6. filtrationAfter filtration and concentration under reduced pressure
  7. customthe residue was recrystallized (n-hexane/ethanol)

Sources & evidence

ORD record
ord-1ede3cf833174c298fc96b0fbb8b4920
Source dataset
uspto-grants-2015_07
Patent number
US09075058B2

Reaction notes

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