Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → tert-butyl (3R,4R)-4-(2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)tetrahydro-2H-pyran-3-ylcarbamate

HRID 246398

반응식

HRID 246398 반응식
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C@@H:26]1[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]1[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36].[CH3:40][O:41][C:42]1[CH:43]=[C:44]2[C:48](=[CH:49][CH:50]=1)[N:47]([CH3:51])[N:46]=[C:45]2[C:52]1[N:53]=[C:54]2[C:60]([C:61](O)=[O:62])=[CH:59][N:58]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])[C:55]2=[N:56][CH:57]=1>CN(C=O)C>[CH3:40][O:41][C:42]1[CH:43]=[C:44]2[C:48](=[CH:49][CH:50]=1)[N:47]([CH3:51])[N:46]=[C:45]2[C:52]1[N:53]=[C:54]2[C:60]([C:61]([NH:25][C@@H:26]3[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]3[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:62])=[CH:59][N:58]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:69])([CH3:71])[CH3:70])[C:55]2=[N:56][CH:57]=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 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamateHCID 712798522-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

생성물 1

HCID 71289100tert-butyl (3R,4R)-4-(2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)tetrahydro-2H-pyran-3-ylcarbamate수율 100%

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 (80.5 mg, 212 μmol.20) and tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (prepared as described in WO2010/97248 A1, 2010; 38.1 mg, 176 μmol) then 2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (80 mg, 176 mmol) dissolved in DMF (2.00 mL) was added to give a light yellow solution which immediately formed a white precipitated. The reaction mixture stirred at 25° C. overnight, solvents evaporated and residue purified by chromatography (60 g column, 50 μm from Analogix, 0 to 5% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane to yield tert-butyl (3R,4R)-4-(2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)tetrahydro-2H-pyran-3-ylcarbamate (115 mg, 176 μmol, 100%) as a very light yellow solid. MS (M+Na)+=674 (>90% purity); 1H NMR (CDCl3) δ: 9.29 (s, 1H), 8.51 (d, J=9.1 Hz, 1H), 8.37 (s, 2H), 7.48 (d, J=9.1 Hz, 1H), 7.31 (dd, J=9.1, 3.0 Hz, 1H), 6.27 (d, J=10.2 Hz, 1H), 5.75 (s, 2H), 4.59-4.81 (m, 1H), 4.18-4.36 (m, 4H), 3.91-4.16 (m, 5H), 3.54-3.81 (m, 4H), 2.33 (qd, J=12.7, 4.9 Hz, 1H), 1.89 (d, J=13.2 Hz, 1H), 0.93-1.12 (m, 2H), 0.82 (s, 9H), 0.00 (s, 9H).

후처리

  1. customIn a 16×100 mm screw cap test tube
  2. additionwas added
  3. customto give a light yellow solution which
  4. customimmediately formed a white precipitated
  5. customsolvents evaporated
  6. customresidue purified by chromatography (60 g column, 50 μm from Analogix, 0 to 5% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane

출처 및 근거

ORD 기록
ord-5fbbdefa63b542f782ab5f9679303ca0
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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