Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-(4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246385노트

반응식

HRID 246385 반응식
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C:26]1([CH2:32][OH:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.[F:34][CH:35]([F:67])[O:36][C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[N:42]([CH3:46])[N:41]=[C:40]2[C:47]1[N:48]=[C:49]2[C:55]([C:56](O)=[O:57])=[CH:54][N:53]([CH2:59][O:60][CH2:61][CH2:62][Si:63]([CH3:66])([CH3:65])[CH3:64])[C:50]2=[N:51][CH:52]=1>CN(C=O)C>[F:67][CH:35]([F:34])[O:36][C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[N:42]([CH3:46])[N:41]=[C:40]2[C:47]1[N:48]=[C:49]2[C:55]([C:56]([NH:25][C:26]3([CH2:32][OH:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[O:57])=[CH:54][N:53]([CH2:59][O:60][CH2:61][CH2:62][Si:63]([CH3:65])([CH3:64])[CH3:66])[C:50]2=[N:51][CH:52]=1

참가 물질

5

반응물 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18316484(4-Aminooxan-4-yl)methanolHCID 712805312-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

생성물 1

HCID 712804842-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-(4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide수율 87.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
25 °C

실험 절차

In a 16×100 mm screw cap test tube were added HATU (34.5 mg, 90.7 μmol.20), (4-aminotetrahydro-2H-pyran-4-yl)methanol (39.7 mg, 302 μmol) and 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (37 mg, 75.6 μmol) then the mixture was dissolved in DMF (3 mL) to give a light yellow solution. The reaction mixture stirred at 25° C. overnight. Solvents evaporated and residue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 5% over 30 min (MeOH containing 10% ammonium hydroxide)/dichloromethane to give 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-(4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (40 mg, 66.4 μmol, 87.8%) as a white solid. MS (M+H)+=603; 1H NMR (CDCl3) δ: 9.19 (s, 1H), 8.45 (s, 1H), 8.36 (s, 1H), 8.07 (d, J=2.3 Hz, 1H), 7.45-7.51 (m, 1H), 7.33 (dd, J=9.1, 2.3 Hz, 1H), 6.55 (t, J=76.0 Hz, 1H), 5.74 (s, 2H), 4.22 (s, 3H), 3.95 (s, 2H), 3.68-3.78 (m, 4H), 3.55-3.66 (m, 2H), 2.11-2.28 (m, 2H), 1.89-2.07 (m, 2H), 0.88-1.04 (m, 2H), −0.02 (s, 9H).

후처리

  1. customIn a 16×100 mm screw cap test tube
  2. customto give a light yellow solution
  3. customSolvents evaporated
  4. customresidue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
  5. washeluting with 0 to 5% over 30 min (MeOH containing 10% ammonium hydroxide)/dichloromethane

출처 및 근거

ORD 기록
ord-669866a6b7d64865a41125dc28762170
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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