Tert-Butylamine → N-tert-butyl-2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246381Notes

Reaction equation

HRID 246381 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]([NH2:29])([CH3:28])[CH3:27].[F:30][CH:31]([F:63])[O:32][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][CH:41]=1)[N:38]([CH3:42])[N:37]=[C:36]2[C:43]1[N:44]=[C:45]2[C:51]([C:52](O)=[O:53])=[CH:50][N:49]([CH2:55][O:56][CH2:57][CH2:58][Si:59]([CH3:62])([CH3:61])[CH3:60])[C:46]2=[N:47][CH:48]=1>CN(C=O)C>[C:26]([NH:29][C:52]([C:51]1[C:45]2[C:46](=[N:47][CH:48]=[C:43]([C:36]3[C:35]4[C:39](=[CH:40][CH:41]=[C:33]([O:32][CH:31]([F:30])[F:63])[CH:34]=4)[N:38]([CH3:42])[N:37]=3)[N:44]=2)[N:49]([CH2:55][O:56][CH2:57][CH2:58][Si:59]([CH3:62])([CH3:61])[CH3:60])[CH:50]=1)=[O:53])([CH3:28])([CH3:27])[CH3:25]

Participants

5

Reactant 3

HCID 6385Tert-Butylamine2×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 71280479N-tert-butyl-2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-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-methylpropan-2-amine (17.9 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 which immediately formed a white precipitated. The reaction mixture stirred at 25° C. overnight. TLC and LCMS showed incomplete reaction, added 2-methylpropan-2-amine (17.9 mg, 245 μmol) and HATU (28.0 mg, 73.5 μmol.20) then 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 N-tert-butyl-2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (33.4 mg, 61.3 μmol, 100%) as an off-white solid. 1H NMR (CDCl3) δ: 9.21 (s, 1H), 8.35 (s, 1H), 8.29 (d, J=2.3 Hz, 1H), 8.04 (s, 1H), 7.44-7.53 (m, 1H), 7.30-7.38 (m, 1H), 7.27 (s, 2H), 6.39 (t, J=74.0 Hz, 1H), 5.72 (s, 2H), 4.21 (s, 3H), 3.50-3.65 (m, 2H), 1.61 (s, 9H), 0.86-1.07 (m, 2H), −0.04 (s, 9H).

Workup

  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. customreaction
  6. waitthe reaction continued at 25° C. for 3 h
  7. customSolvents evaporated
  8. customresidue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
  9. washeluting with 0 to 50% EtOAc in hexanes over 30 min

Sources & evidence

ORD record
ord-f59783ce6032463f8fcb38d235a80336
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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