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4-Methylmorpholine → (R)-tert-butyl 2-(6-fluoro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoate

HRID 1968258
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HRID 1968258 반응식
[C:1]([O:5][C:6](=[O:36])[C@H:7]([NH:11][CH2:12][C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15]2[N:20]([S:26]([C:29]3[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[CH:21]=[C:22]([C:23]([OH:25])=O)[C:14]=12)[CH:8]([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>>[F:19][C:18]1[C:13]2[CH2:12][N:11]([C@H:7]([CH:8]([CH3:10])[CH3:9])[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:36])[C:23](=[O:25])[C:22]3=[CH:21][N:20]([S:26]([C:29]4[CH:30]=[CH:31][C:32]([CH3:33])=[CH:34][CH:35]=4)(=[O:28])=[O:27])[C:15]([C:14]=23)=[N:16][CH:17]=1
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참가 물질

4

반응물 3

HCID 79724-Methylmorpholine2회HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2회HCID 58293452(R)-4-((1-tert-butoxy-3-methyl-1-oxobutan-2-ylamino)methyl)-5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid

생성물 1

HCID 58293424(R)-tert-butyl 2-(6-fluoro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoate

실험 절차

Crude (R)-4-((l-tert-butoxy-3-methyl-1-oxobutan-2-ylamino)methyl)-5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid was heated in HATU (2.60 g, 7.19 mmol) and 4-methylmorpholine (1.091 g, 10.79 mmol) at reflux for 3 h. The reaction was incomplete by LC-MS. HATU (1.37 g, mmol, 3.79 mmol) and 4-methylmorpholine (1.091 g, 10.79 mmol) were added and the reaction mixture was stirred at reflux for 16 h. Following reaction, the mixture was washed with aqueous NaHCO3 (sat.) and extracted with DCM. The organics were washed with brine, dried over Na2SO4, and concentrated to a brown oil. Purification by silica column chromatography (EtOAc/DCM, 0-20%) afforded the title compound as a white foam. (0.933 g, 51.7%). 1H NMR (400 MHz, DMSO-d6) δ 0.80 (d, J=6.57 Hz, 3 H) 1.02 (d, J=6.57 Hz, 3 H) 1.39 (s, 9 H) 2.31-2.39 (m, 4 H) 4.77 (d, J=10.61 Hz, 1 H) 5.02 (d, J=7.58 Hz, 2 H) 7.46 (d, J=7.83 Hz, 2 H) 8.08 (d, J=8.34 Hz, 2 H) 8.29 (s, 1 H) 8.44 (d, J=2.78 Hz, 1 H). [M+H] calc'd for C25H28FN3O5S, 502; found, 502.3.

후처리

  1. temperatureat reflux for 16 h
  2. customreaction
  3. washthe mixture was washed with aqueous NaHCO3 (sat.)
  4. extractionextracted with DCM
  5. washThe organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to a brown oil
  8. customPurification by silica column chromatography (EtOAc/DCM, 0-20%)

출처 및 근거

ORD 기록
ord-5dfffc34be014df1b742af04e01f41f1
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08420816B2

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