5-Methylpyrazin-2-amine → (S)-2-(tert-butyldimethylsilyloxy)-3-((S)-1-methoxypropan-2-yloxy)-N-(5-methylpyrazin-2-yl)propanamide

HRID 1098152노트

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HRID 1098152 반응식
C[Al](C)C.[CH3:5][C:6]1[N:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.[Si:13]([O:20][C@@H:21]([CH2:26][O:27][C@@H:28]([CH3:32])[CH2:29][O:30][CH3:31])[C:22](OC)=[O:23])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Si:13]([O:20][C@@H:21]([CH2:26][O:27][C@@H:28]([CH3:32])[CH2:29][O:30][CH3:31])[C:22]([NH:12][C:9]1[CH:8]=[N:7][C:6]([CH3:5])=[CH:11][N:10]=1)=[O:23])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:14])[CH3:15]

참가 물질

7

반응물 4

HCID 3132155-Methylpyrazin-2-amineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 59279557(S)-methyl 2-(tert-butyldimethylsilyloxy)-3-((S)-1-methoxypropan-2-yloxy)propanoate

생성물 1

HCID 57504629(S)-2-(tert-butyldimethylsilyloxy)-3-((S)-1-methoxypropan-2-yloxy)-N-(5-methylpyrazin-2-yl)propanamide수율 31%

시약·촉매·용매 2

HCID 1140Toluene용매2회HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

Trimethylaluminium (2M in hexane) (1.126 mL, 2.25 mmol) was added dropwise to 5-methylpyrazin-2-amine (214 mg, 1.96 mmol) in toluene (5 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred for 20 minutes. A solution of (S)-methyl 2-(tert-butyldimethylsilyloxy)-3-((S)-1-methoxypropan-2-yloxy)propanoate (Intermediate Y1) (600 mg, 1.96 mmol) in toluene (2 mL) was added to the reaction mixture and the resulting solution was stirred at reflux for 5 hours. The reaction was allowed to cool to RT before adding ethyl acetate (30 mL) and 20% sodium potassium tartrate solution (30 mL), which was stirred vigorously for 16 hours. The phases were separated and the organic layer was washed with sat. brine (15 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 60% ethyl acetate in isohexane to afford the product (230 mg, 31%). 1H NMR (400 MHz, CDCl3) 6 0.17 (d, 6H), 0.98 (s, 9H), 1.16 (d, 3H), 2.53 (s, 3H), 3.25-3.32 (m, 4H), 3.35-3.42 (m, 1H), 3.60-3.68 (m, 1H), 3.74-3.80 (m, 1H), 3.82-3.87 (m, 1H), 4.35-4.40 (m, 1H), 8.12-8.13 (m, 1H), 8.98 (s, 1H), 9.42 (d, 1H); m/z (ESI+) (M+H)+=384.23; HPLC tR=10.70 min.

후처리

  1. stirringthe resulting solution was stirred
  2. temperatureat reflux for 5 hours
  3. temperatureto cool to RT
  4. stirringwas stirred vigorously for 16 hours
  5. customThe phases were separated
  6. washthe organic layer was washed with sat. brine (15 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe crude product was purified by flash silica chromatography
  10. washeluting with 0 to 60% ethyl acetate in isohexane

출처 및 근거

ORD 기록
ord-ddab966bba5c4b45a76b7fa9624172ec
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08143263B2

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