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Dimethylamine → 2-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)-N,N-dimethylacetamide

HRID 1052265
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HRID 1052265 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][C:13]2[N:14]=[C:15]3[CH:21]=[C:20]([C:22]4[CH:23]=[N:24][N:25]([CH2:27][C:28]([OH:30])=O)[CH:26]=4)[N:19](S(C4C=CC=CC=4)(=O)=O)[C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[CH3:40][NH:41][CH3:42].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([CH2:11][CH2:12][C:13]2[N:14]=[C:15]3[CH:21]=[C:20]([C:22]4[CH:23]=[N:24][N:25]([CH2:27][C:28]([N:41]([CH3:42])[CH3:40])=[O:30])[CH:26]=4)[NH:19][C:16]3=[N:17][CH:18]=2)[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
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HCID 674DimethylamineHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89963529{4-[2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]-1H-pyrazol-1-yl}acetic acid

생성물 1

HCID 73056840
2-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)-N,N-dimethylacetamide
수율 35.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

To a stirred solution of {4-[2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazin-6-yl]-1H-pyrazol-1-yl}acetic acid (10.0 mg, 18.3 μmol) in N,N-dimethylformamide (1.0 mL), N,N-dimethylamine (2.0 M in THF, 13.7 μL, 27.4 μmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (8.33 mg, 21.9 mmol) and N,N-diisopropylethylamine (12.7 μL, 73.0 μmol) were added sequentially at ambient temperature. After 1 hour, the reaction was quenched with saturated aqueous NH4Cl, extracted with methylene chloride. The combined organic layers were dried over MgSO4, and then concentrated. The residue was dissolved in methanol (2.0 mL) and potassium carbonate (5.05 mg, 36.5 μmol) was added. The reaction mixture was then warmed up to 60° C. After 2 hours, the crude mixture was cooled to ambient temperature and purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (2.8 mg) as its TFA salt. LCMS calculated for C23H27N6O3 (M+H)+: m/z=435.2. Found: 435.3.

후처리

  1. customthe reaction was quenched with saturated aqueous NH4Cl
  2. extractionextracted with methylene chloride
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in methanol (2.0 mL)
  6. waitAfter 2 hours
  7. custompurified on RP-HPLC (XBridge C18 column
  8. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min)

출처 및 근거

ORD 기록
ord-bdb324f9aae7439fa8f72b6935004bed
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09388185B2

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