2-Amino-2-methyl-1-propanol → 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246383Notes

Reaction equation

HRID 246383 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C:26]([CH3:30])([CH3:29])[CH2:27][OH:28].[F:31][CH:32]([F:64])[O:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[N:39]([CH3:43])[N:38]=[C:37]2[C:44]1[N:45]=[C:46]2[C:52]([C:53](O)=[O:54])=[CH:51][N:50]([CH2:56][O:57][CH2:58][CH2:59][Si:60]([CH3:63])([CH3:62])[CH3:61])[C:47]2=[N:48][CH:49]=1>CN(C=O)C>[F:64][CH:32]([F:31])[O:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[N:39]([CH3:43])[N:38]=[C:37]2[C:44]1[N:45]=[C:46]2[C:52]([C:53]([NH:25][C:26]([CH3:30])([CH3:29])[CH2:27][OH:28])=[O:54])=[CH:51][N:50]([CH2:56][O:57][CH2:58][CH2:59][Si:60]([CH3:62])([CH3:61])[CH3:63])[C:47]2=[N:48][CH:49]=1

Participants

5

Reactant 3

HCID 118072-Amino-2-methyl-1-propanol2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 712805312-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 712802362-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

In a 16×100 mm screw cap test tube were added HATU (28.0 mg, 73.5 μmol.20) and 2-amino-2-methylpropan-1-ol (21.8 mg, 245 μmol) then 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (30 mg, 61.3 μmol) dissolved in DMF (2.00 mL) was added to give a light yellow solution. The reaction mixture stirred at 25° C. overnight. TLC and LCMS showed incomplete reaction added 2-amino-2-methylpropan-1-ol (21.8 mg, 245 μmol) and HATU (28.0 mg, 73.5 μmol) and the reaction continued at 25° C. for 3 h. Solvents evaporated and residue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 50% EtOAc in hexanes over 30 min to yield 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (34.4 mg, 61.3 μmol, 100%) as an off-white solid. 1H NMR (CDCl3) δ: 9.22 (s, 1H), 8.35 (s, 1H), 8.31 (s, 1H), 8.24 (d, J=2.3 Hz, 1H), 7.43-7.52 (m, 1H), 7.34 (dd, J=8.9, 2.1 Hz, 1H), 6.53 (t, J=75.0 Hz, 1H), 5.72 (s, 2H), 4.21 (s, 3H), 3.79 (s, 2H), 3.53-3.64 (m, 2H), 1.55 (s, 6H), 0.85-1.07 (m, 2H), −0.03 (s, 9H).

Workup

  1. customIn a 16×100 mm screw cap test tube
  2. additionwas added
  3. customto give a light yellow solution
  4. customreaction
  5. waitthe reaction continued at 25° C. for 3 h
  6. customSolvents evaporated
  7. customresidue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
  8. washeluting with 0 to 50% EtOAc in hexanes over 30 min

Sources & evidence

ORD record
ord-7bff85c3b1ce4f1b85168bceeea783e6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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